Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment - Schmidt, Eva; Distel, Luitpold; Erber, Ramona; Büttner-Herold, Maike; Rosahl, Marie-Charlotte; Ott, Oliver; Strnad, Vratislav; Hack, Carolin; Hartmann, Arndt; Hecht, Markus; Fietkau, Rainer; Schnellhardt, Sören (Cancers, 2024)
Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage hormone-receptor-positive breast cancer as part of an Accelerated Partial Breast Irradiation (APBI) phase II trial. Resection samples from multiple locations were processed into tissue microarrays and sections thereof immunohistochemically stained for CD66b+ neutrophils. CD66b+ neutrophil density was measured separately in the stromal and intraepithelial compartment. Results: High stromal and intraepithelial CD66b+ TAN density was a negative prognostic factor in central tumor samples. In addition, neutrophil density in adjacent normal breast tissue and lymph node samples also correlated with reduced disease-free survival. TAN density correlated with CD163+ M2-like tumor-associated macrophage (TAM) density, which we analyzed in a previous study. TANs were a negative prognostic factor in tumors with an elevated M1/M2 TAM ratio, while this impact on patient outcome was lost in tumors with a low M1/M2 ratio. A combined multivariate analysis of TAM and TAN density revealed that only TAM polarization status was an independent prognostic factor. Conclusions: CD66b+ neutrophils were a negative prognostic factor in early-stage luminal breast cancer in single-marker analysis. Combined analysis with TAMs could be necessary to correctly evaluate their prognostic impact in future studies. TAN recruitment might act as a compensatory mechanism of immunoevasion and disease progression in tumors that are unable to sufficiently attract and polarize TAMs.
CRIS-Team Scopus Importer:2024-10-11
Keywords: breast cancer; CD66b; luminal; tumor-associated macrophages; tumor-associated neutrophils

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

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

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

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

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

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

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

Understanding the genetic complexity of puberty timing across the allele frequency spectrum - Kentistou, Katherine A.; Kaisinger, Lena R.; Stankovic, Stasa; Vaudel, Marc; Mendes de Oliveira, Edson; Messina, Andrea; Walters, Robin G.; Liu, Xiaoxi; Busch, Alexander S.; Helgason, Hannes; Thompson, Deborah J.; Santoni, Federico; et al. (Nature Genetics, 2024)
Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on 800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited 11 and 14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in 200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
CRIS-Team Scopus Importer:2024-07-26

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

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

Update Breast Cancer 2019 Part 2-Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice - Janni, Wolfgang; Schneeweiss, Andreas; Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin-Andrei; Tesch, Hans; Overkamp, Friedrich; Lueftner, Diana; Belleville, Erik; et al. (Geburtshilfe und Frauenheilkunde, 2019)
The treatment of patients with advanced breast cancer has developed further in recent years. In addition to therapeutic progress in the established subgroups (hormone receptor and HER2 status), there are now therapies which are geared to individual molecular characteristics, such as PARP inhibitor therapy in BRCA-mutated patients. In addition to this, tests are being developed which are intended to establish addition-al markers within subgroups in order to predict the efficacy of a therapy. PI3K mutation testing in HER2-negative, hormonereceptor- positive tumours and PD-L1 testing of immune cells in triple-negative tumours are expected to become established in clinical practice in order to select patients for the respective therapies. With new therapeutic approaches, new adverse effects also appear. The management of these adverse effects, just as those of classical therapy (supportive therapy), is essential with the introduction of new treatments in order to preserve patients ' quality of life. Knowledge regarding measures to preserve and improve quality of life has significantly increased in recent years. Lifestyle factors should be taken into account, as should modern therapeutic methods. This review summarises the latest studies and publications and evaluates them in regard to the relevance for clinical practice.
CRIS-Team WoS Importer:2019-04-02

Update Breast Cancer 2019 Part 2 - Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice Update Mammakarzinom 2019 Teil 2 - Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis - Janni, Wolfgang; Schneeweiss, Andreas; Müller, Volkmar; Wöckel, Achim; Lux, Michael P.; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin Andrei; Tesch, Hans; Overkamp, Friedrich; Lüftner, Diana; Belleville, Erik; et al. (TumorDiagnostik & Therapie, 2019)
The treatment of patients with advanced breast cancer has developed further in recent years. In addition to therapeutic progress in the established subgroups (hormone receptor and HER2 status), there are now therapies which are geared to individual molecular characteristics, such as PARP inhibitor therapy in BRCA-mutated patients. In addition to this, tests are being developed which are intended to establish additional markers within subgroups in order to predict the efficacy of a therapy. PI3K mutation testing in HER2-negative, hormonereceptor-positive tumours and PDâ€ L1 testing of immune cells in triple-negative tumours are expected to become established in clinical practice in order to select patients for the respective therapies. With new therapeutic approaches, new adverse effects also appear. The management of these adverse effects, just as those of classical therapy (supportive therapy), is essential with the introduction of new treatments in order to preserve patientsÊ¼ quality of life. Knowledge regarding measures to preserve and improve quality of life has significantly increased in recent years. Lifestyle factors should be taken into account, as should modern therapeutic methods. This review summarises the latest studies and publications and evaluates them in regard to the relevance for clinical practice.
CRIS-Team Scopus Importer:2019-09-17
Keywords: advanced; alpelisib; atezolizumab; breast cancer; metastatic; PARP; PD-L1; PI3K; supportive therapy

Update Breast Cancer 2019 Part 3 - Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel - Kolberg, Hans Christian; Schneeweiss, Andreas; Fehm, Tanja N.; Wöckel, Achim; Huober, Jens; Pontones, Constanza; Titzmann, Adriana; Belleville, Erik; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Taran, Florin Andrei; et al. (Geburtshilfe und Frauenheilkunde, 2019)
The treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.
CRIS-Team Scopus Importer:2019-06-04
Keywords: adjuvant therapy; early breast cancer; neoadjuvant therapy; St. Gallen panel of experts

Update Breast Cancer 2019 Part 3 - Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel Update Mammakarzinom 2019 Teil 3 - aktuelle Entwicklungen bei der kurativen Behandlung von Mammakarzinom-Patientinnen: Eine Übersicht und Bewertung durch ein internationales Expertenpanel - Kolberg, Hans Christian; Schneeweiss, Andreas; Fehm, Tanja N.; Wöckel, Achim; Huober, Jens; Pontones, Constanza; Titzmann, Adriana; Belleville, Erik; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Taran, Florin Andrei; et al. (TumorDiagnostik & Therapie, 2019)
The treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.
CRIS-Team Scopus Importer:2019-09-17
Keywords: adjuvant therapy; early breast cancer; neoadjuvant therapy; St. Gallen panel of experts

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

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

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

Update Breast Cancer 2020 Part 3 - Early Breast Cancer - Huober, Jens; Schneeweiss, Andreas; Hartkopf, Andreas D.; Müller, Volkmar; Lux, Michael P.; Janni, Wolfgang; Ettl, Johannes; Belleville, Erik; Thill, Marc; Fasching, Peter; Kolberg, Hans Christian; Schulmeyer, Carla; et al. (Geburtshilfe und Frauenheilkunde, 2020)
The treatment of patients with early breast cancer has always been characterised by escalation by new therapies and de-escalation through identification of better treatment regimens or introduction of better tools to estimate prognosis. Efforts in some of these areas in the last few years have led to solid data. The results of the large studies of de-escalation through use of multi-gene tests are available, as are the results of some studies that investigated the new anti-HER2 substances T-DM1 and pertuzumab in the early treatment situation. Several large-scale studies examining the role of CDK4/6 inhibitors will soon be concluded so innovations can be anticipated in this area also. This review article will summarise and classify the results of the latest publications.
CRIS-Team Scopus Importer:2020-11-27
Keywords: digital medicine; early breast cancer; immunotherapy; prevention; prognosis; treatment

Update Breast Cancer 2020 Part 4 – Advanced Breast Cancer - Tesch, Hans; Müller, Volkmar; Wöckel, Achim; Ettl, Johannes; Belleville, Erik; Schütz, Florian; Hartkopf, Andreas; Thill, Marc; Huober, Jens; Fasching, Peter; Kolberg, Hans Christian; Schulmeyer, Carla E.; et al. (Geburtshilfe und Frauenheilkunde, 2020)
Substances with good effectiveness that intervene in specific signalling pathways have been used increasingly in recent years in the treatment of patients with advanced breast cancer, and new therapies and approaches have now been added, which actually relate to quite specific changes, such as the treatment of patients with HR+/HER2 tumours with a PIK3CA mutation. The treatment of patients with a BRCA1 or BRCA2 mutation has also been improved by the introduction of PARP inhibitors. Attempts are now being made increasingly to extend treatment indications based on molecular patterns, to identify other patients who could benefit from a treatment and to integrate the newly established treatment methods in existing therapy sequences. This review articles summarises the latest information in this connection.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Advanced breast cancer; BRCA1/2; CDK4/6; immunotherapy; metastases; mutation testing; PARP; PD-L1; treatment

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

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

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

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

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

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

Update Breast Cancer 2022 Part 1 - Early Stage Breast Cancer. - Welslau, Manfred; Mueller, Volkmar; Lueftner, Diana; Schuetz, Florian; Stickeler, Elmar; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Fehm, Tanja N.; Belleville, Erik; Bader, Simon; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Evidence relating to the treatment of breast cancer patients with early-stage disease has increased significantly in the past year. Abemaciclib, olaparib, and pembrolizumab are new drugs with good efficacy in the relevant patient groups. However, some questions remain unanswered. In particular, it remains unclear which premenopausal patients with hormone receptor-positive breast cancer should be spared unnecessary treatment. The question of the degree to which chemotherapy exerts a direct cytotoxic effect on the tumor or reduces ovarian function through chemotherapy could be of key importance. This group of patients could potentially be spared chemotherapy. New, previously experimental biomarker analysis methods, such as spatial analysis of gene expression (spatial transcriptomics) are gradually finding their way into large randomized phase III trials, such as the NeoTRIP trial. This in turn leads to a better understanding of the predictive factors of new therapies, for example immunotherapy. This review summarizes the scientific innovations from recent congresses such as the San Antonio Breast Cancer Symposium 2021 but also from recent publications.
EVALuna2:511215

Update Breast Cancer 2022 Part 2 - Advanced Stage Breast Cancer - Müller, Volkmar; Welslau, Manfred; Lüftner, Diana; Schütz, Florian; Stickeler, Elmar; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Fehm, Tanja N.; Belleville, Erik; Bader, Simon; et al. (Geburtshilfe und Frauenheilkunde, 2022)
For patients with advanced breast cancer, several novel therapies have emerged in recent years, including CDK4/6 inhibitors, immune checkpoint inhibitors, PARP inhibitors, alpelisib, tucatinib and trastuzumab-deruxtecan, and sacituzumab-govitecan, which have transformed and expanded the therapeutic landscape for patients with advanced breast cancer. Some of these substances have now been approved for use in the early stages of the disease, or are expected to be approved in the near future, so the therapeutic landscape will change once again. Therefore, current scientific efforts are focused on the introduction of new substances and understanding their mechanisms of progression and efficacy. This review summarizes recent developments with reference to recent publications and conferences. Findings on the treatment of patients with HER2-positive breast cancer and brain metastases are presented, as are a number of studies looking at biomarkers in patients with HER2-negative, hormone receptor-positive breast cancer. In particular, the introduction of oral selective estrogen receptor degraders provides new opportunities to establish biomarker-based therapy. Molecular diagnostics is establishing itself as a diagnostic marker and parameter of progression.
CRIS-Team Scopus Importer:2022-08-05
Keywords: ADC; biomarker; breast cancer; metastatic; PD-L1

Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer. - Fehm, Tanja N.; Welslau, Manfred; Mueller, Volkmar; Lueftner, Diana; Schuetz, Florian; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Belleville, Erik; Untch, Michael; Thill, Marc; et al. (Geburtshilfe und Frauenheilkunde, 2022)
This review summarizes recent developments in the prevention and treatment of patients with early-stage breast cancer. The individual disease risk for different molecular subtypes was investigated in a large epidemiological study. With regard to treatment, new data are available from long-term follow-up of the Aphinity study, as well as new data on neoadjuvant therapy with atezolizumab in HER2-positive patients. Biomarkers, such as residual cancer burden, were investigated in the context of pembrolizumab therapy. A Genomic Grade Index study in elderly patients is one of a group of studies investigating the use of modern multigene tests to identify patients with an excellent prognosis in whom chemotherapy may be avoided. These and other aspects of the latest developments in the diagnosis and treatment of breast cancer are described in this review.
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Update Breast Cancer 2022 Part 4 - Advanced-Stage Breast Cancer. - Aktas, Bahriye; Fehm, Tanja N.; Welslau, Manfred; Mueller, Volkmar; Lueftner, Diana; Schuetz, Florian; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Belleville, Erik; Untch, Michael; et al. (Geburtshilfe und Frauenheilkunde, 2022)
For the treatment of patients with advanced HER2-negative hormone receptor-positive breast cancer, several substances have been introduced into practice in recent years. In addition, other drugs are under development. A number of studies have been published over the past year which have shown either an advantage for progression-free survival or for overall survival. This review summarizes the latest results, which have been published at current congresses or in specialist journals, and classifies them in the clinical treatment context. In particular, the importance of therapy with CDK4/6 inhibitors - trastuzumab deruxtecan, sacituzumab govitecan and capivasertib - is discussed. For trastuzumab deruxtecan, an overall survival benefit in HER2-negative breast cancer with low HER2 expression (HER2-low expression) was reported in the Destiny-Breast-04 study. Similarly, there was an overall survival benefit in the FAKTION study with capivasertib. The lack of overall survival benefit for palbociclib in the first line of therapy raises the question of clinical classification.
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Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer - Fehm, Tanja N.; Welslau, Manfred; Müller, Volkmar; Lüftner, Diana; Schütz, Florian; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Beierlein, Milena; Belleville, Erik; Untch, Michael; et al. (Geburtshilfe und Frauenheilkunde, 2023)
The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies.
CRIS-Team Scopus Importer:2023-03-31
Keywords: breast cancer; chemotherapy; surgery; therapy standard

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

Update Breast Cancer 2023 Part 2 - Advanced-Stage Breast Cancer. - Lux, Michael P.; Hartkopf, Andreas D.; Fehm, Tanja N.; Welslau, Manfred; Müller, Volkmar; Schütz, Florian; Fasching, Peter; Janni, Wolfgang; Witzel, Isabell; Thomssen, Christoph; Beierlein, Milena; Belleville, Erik; et al. (Geburtshilfe und Frauenheilkunde, 2023)
In recent years, a number of new therapies have led to advances in the treatment of patients with advanced breast carcinoma. These substances are mainly CDK4/6 inhibitors and other substances that can overcome endocrine resistance, oral selective estrogen receptor degraders, antibody drug conjugates (ADCs), and PARP inhibitors. This review summarizes and evaluates the latest study results that have been published in recent months. This includes the overall survival data of the Destiny-Breast03 study, the first analysis of the CAPItello-291 study, the comparison of CDK4/6 inhibitor treatment with chemotherapy in the first line of therapy (RIGHT Choice study), the first analysis of the Destiny-Breast02 study in the treatment setting after T-DM1 treatment, and the first analysis of the Serena-2 study. Most of these studies have the potential to significantly change the therapeutic landscape for patients with advanced breast carcinoma and show that the continued rapid development of new therapies is always producing new results.
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Update Breast Cancer 2024 Part 1 - Expert Opinion on Advanced Breast Cancer - Würstlein, Rachel; Kolberg, Hans Christian; Hartkopf, Andreas D.; Fehm, Tanja N.; Welslau, Manfred; Schütz, Florian; Fasching, Peter; Janni, Wolfgang; Witzel, Isabell; Thomssen, Christoph; Krückel, Annika; Belleville, Erik; et al. (Geburtshilfe und Frauenheilkunde, 2024)
Clinical evidence is interpreted based on clinical studies and personal experience which can lead to different interpretations of data. This makes the opinions issued by panels of experts such as the Advanced Breast Cancer Panel which convened in November 2023 for the seventh time (ABC7) particularly important. At the conference, current issues around advanced breast cancer were evaluated by an international team of experts.In 2023 the data on CDK4/6 inhibitors was so extensive that the answers to questions about the sequencing of therapy and the potential use of chemotherapy as an alternative therapy were relatively clear. Moreover, data on antibody drug conjugates which provides a good overview of their uses is available for all molecular subtypes.Some therapeutic settings, including patients with brain metastases or leptomeningeal disease, older patients, locally advanced breast cancer and visceral crises, continue to be particularly important and were discussed in structured sessions. The scientific context of some of the topics discussed at ABC7 is presented and assessed here.
CRIS-Team Scopus Importer:2024-06-14
Keywords: antibody drug conjugate; breast cancer; chemotherapy; endocrine therapy; metastatic

Update Breast Cancer 2024 Part 2-Patients with Early Stage Breast Cancer Update Mammakarzinom 2024 Teil 2 – Patientinnen mit Frühstadien des Mammakarzinoms - Janni, Wolfgang; Kolberg, Hans Christian; Hartkopf, Andreas D.; Fehm, Tanja N.; Welslau, Manfred; Müller, Volkmar; Schütz, Florian; Fasching, Peter; Jackisch, Christian; Marme, Frederik; Hörner, Manuel; Keller, Katharina; et al. (Geburtshilfe und Frauenheilkunde, 2025)
This review summarizes the latest developments for the treatment of patients with early-stage breast cancer. Most of the clinically relevant changes were the result of using immune checkpoint inhibitors to treat patients with triple-negative breast cancer (TNBC) and CDK4/6 inhibitors to treat patients with hormone receptor-positive, HER2-negative (HRpos/HER2neg) tumors and a high risk of recurrence. Recent studies are presenting more and more data with long follow-up times and integrating translational analyses to evaluate new biomarkers such as circulating tumor DNA (ctDNA). This review article summarizes the latest developments published in recent months and puts the findings in context.
CRIS-Team Scopus Importer:2025-05-30
Keywords: biomarker; breast cancer; clinical studies; early breast cancer

Update Breast Cancer 2024 Part 3-Patients with Advanced Stage Breast Cancer Update Mammakarzinom 2024 Teil 3 – Patientinnen mit fortgeschrittenen Stadien des Mammakarzinoms - Lüftner, Diana; Kolberg, Hans Christian; Hartkopf, Andreas D.; Fehm, Tanja N.; Welslau, Manfred; Müller, Volkmar; Schütz, Florian; Fasching, Peter; Jackisch, Christian; Marme, Frederik; Keller, Katharina; Hörner, Manuel; et al. (Geburtshilfe und Frauenheilkunde, 2025)
The use of CDK4/6 inhibitors, the new PI3K/AKT-kinase inhibitors, selective estrogen receptor-degraders (SERDs), antibody-drug conjugates, immune therapies and PARP inhibitors in recent years has resulted in a marked change in the therapy landscape for patients with advanced stage breast cancer. CDK4/6 inhibitors, trastuzumab deruxtecan, and sacituzumab govitecan have all been shown to provide significant overall survival benefits compared to conventional chemotherapy. Other substances are also showing promising results and hold out the hope that further analysis of the overall survival benefits will be available in the near future. The speed at which studies are now being carried out has markedly increased, and conferences and specialist journals are now constant sources of new information. This review summarizes the most recent publications and conference presentations on the treatment of patients with advanced stage breast cancer.
CRIS-Team Scopus Importer:2025-05-30
Keywords: advanced breast cancer; breast cancer; clinical studies; prognosis

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

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

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

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

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

Updates on the role of receptor activator of nuclear factor κB/receptor activator of nuclear factor κB ligand/osteoprotegerin pathway in breast cancer risk and treatment - Bayer, Christian M.; Beckmann, Matthias; Fasching, Peter (Current Opinion in Obstetrics & Gynecology, 2017)
PURPOSE OF REVIEW: Treatment with bisphosphonates and denosumab is the standard of care in bone metastatic disease. In addition, the adjuvant therapy of denosumab or bisphosphonates is very effective to prevent loss of bone mineral density, for example in osteoporosis. However, it is still unclear if this therapy has an influence on preventing cancer. RECENT FINDINGS: Since the identification of novel genes in the 1980s, it took about 30 years until denosumab, as a fully human mAb against receptor activator of nuclear factor (NF)-κB ligand (RANKL), could be introduced to clinical practice. The discovery of the receptor activator of NF-κB/RANKL/osteoprotegerin pathway in the 1990s is an example of how modern databases of genes were utilized to discover new pathways relevant to a variety of diseases. The essential role of this pathway for the function, differentiation and survival of osteoclasts, and the influence on the bone microenvironment helped to understand the vicious circle of bone resorption and destruction in many skeletal diseases. SUMMARY: In the following review, we discuss the important role of rational targeting concerning receptor activator of NF-κB/RANKL/osteoprotegerin and the bisphosphonate therapy and provide an update for the related treatment of patients suffering from breast cancer and further implications for clinical practice and research using denosumab as a potential chemoprevention in BRCA1-related breast cancer.
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Ureterocele as differential diagnosis of hydrosalpinx-an interesting case from the clinical practice - Psilopatis, Iason; Beckmann, Matthias; Emons, Julius; Schulmeyer, Carla (Journal of Surgical Case Reports, 2024)
Hydrosalpinx is a common condition in women of reproductive age that correlates with infertility. A ureterocele is a dilatation of the terminal ureter within the bladder and/or urethra that occurs seldomly in adults, but can sonographically be mistaken for a hydrosalpinx.We report of a 29-year-old patient (G2/P1) who was referred in our department with secondary infertility and suspicion of hydrosalpinx.Intraoperatively,no hydrosalpinx could be visualized.Postoperatively,an intravesical cystic mass was detected,alongside a second-degree urinary retention. Sonographically, a double kidney on the left side and an accentuated calyx system could be diagnosed. Ureteroceles seem to represent a rare but still possible differential diagnosis in suspected hydrosalpinx, given the similar sonographic presentation of both conditions.
CRIS-Team Scopus Importer:2024-04-26
Keywords: hydrosalpinx; infertility; ureterocele

Usability and Perception of a Wearable-Integrated Digital Maternity Record App in Germany: User Study - Nissen, Michael; Perez, Carlos A.; Jäger, Katharina; Bleher, Hannah; Flaucher, Madeleine; Hübner, Hanna; Danzberger, Nina; Titzmann, Adriana; Pontones, Constanza; Fasching, Peter; Beckmann, Matthias; Eskofier, Björn; et al. (JMIR Pediatrics and Parenting, 2023)
Background: Although digital maternity records (DMRs) have been evaluated in the past, no previous work investigated usability or acceptance through an observational usability study. Objective: The primary objective was to assess the usability and perception of a DMR smartphone app for pregnant women. The secondary objective was to assess personal preferences and habits related to online information searching, wearable data presentation and interpretation, at-home examination, and sharing data for research purposes during pregnancy. Methods: A DMR smartphone app was developed. Key features such as wearable device integration, study functionalities (eg, questionnaires), and common pregnancy app functionalities (eg, mood tracker) were included. Women who had previously given birth were invited to participate. Participants completed 10 tasks while asked to think aloud. Sessions were conducted via Zoom. Video, audio, and the shared screen were recorded for analysis. Task completion times, task success, errors, and self-reported (free text) feedback were evaluated. Usability was measured through the System Usability Scale (SUS) and User Experience Questionnaire (UEQ). Semistructured interviews were conducted to explore the secondary objective. Results: A total of 11 participants (mean age 34.6, SD 2.2 years) were included in the study. A mean SUS score of 79.09 (SD 18.38) was achieved. The app was rated “above average” in 4 of 6 UEQ categories. Sixteen unique features were requested. We found that 5 of 11 participants would only use wearables during pregnancy if requested to by their physician, while 10 of 11 stated they would share their data for research purposes. Conclusions: Pregnant women rely on their medical caregivers for advice, including on the use of mobile and ubiquitous health technology. Clear benefits must be communicated if issuing wearable devices to pregnant women. Participants that experienced pregnancy complications in the past were overall more open toward the use of wearable devices in pregnancy. Pregnant women have different opinions regarding access to, interpretation of, and reactions to alerts based on wearable data. Future work should investigate personalized concepts covering these aspects.
Created from Fastlane, Scopus look-up
Keywords: app; application; applications; apps; attitude; attitudes; data sharing; develop; development; digital; electronic; electronic maternity record; experience; experiences; feature; features; health record; health records; information behavior; information behaviour; information seeking; log; logbook; maternal; maternity; maternity log; maternity logbook; maternity record; mHealth; mobile health; online search; opinion; opinions; paper hand-held record; perception; perceptions; personal health record; perspective; perspectives; PHR; pregnancy; pregnancy app; pregnancy record; pregnant; privacy; searching; smartphone; smartphones; usability; wearable; wearables

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

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

Use of Granulocyte-colony Stimulating Factor During Chemotherapy and Its Association With CA27.29 and Circulating Tumor Cells-Results From the SUCCESS A Trial - Hepp, Philip; Fasching, Peter; Beckmann, Matthias; Fehm, Tanja; Salmen, Jessica; Hagenbeck, Carsten; Jaeger, Bernadette; Widschwendter, Peter; De Gregorio, Nikolaus; Schochter, Fabienne; Mahner, Sven; Harbeck, Nadia; et al. (Clinical Breast Cancer, 2018)
Little is known about the effect of granulocyte colony-stimulating factor (G-CSF) treatment during adjuvant chemotherapy on prognostic markers. The present study explored the association between G-CSF and changes in cancer antigen (CA)27.29 and circulating tumor cell (CTC) levels during therapy.A total of 3754 node-positive or high-risk node-negative early-stage breast cancer patients were treated within the SUCCESS-A trial (simultaneous study of gemcitabine-docetaxel combination adjuvant treatment, as well as extended bisphosphonate and surveillance-trial). CA27.29 and CTCs were determined before the start and within 6 weeks after the end of chemotherapy.Overall, 1324 of the 2646 patients (50.0%) available for analysis had >= 1 G-CSF applications during chemotherapy. G-CSF application was significantly associated with CA27.29 status before and after chemotherapy (? = 30.6, df = 3; P < .001), because 238 patients (18.0%) with G-CSF treatment but only 146 (11.0%) without G-CSF treatment switched from a negative CA27.29 status before to a positive CA27.29 status after chemotherapy. In addition, patients with G-CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy compared with patients without any G-CSF application during chemotherapy (Mann-Whitney U test; Z = -7.81, P < .001). No significant association was found between G-CSF application and CTC status before or after chemotherapy (? = 1.2, df = 3; P = .75).Cautious interpretation is needed regarding elevated levels of MUC-1-derived tumor markers such as CA27.29 shortly after adjuvant chemotherapy when G-CSF has been given, because G-CSF treatment was associated with increased CA27.29 levels after chemotherapy.
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Using automated texture features to determine the probability for masking of a tumor on mammography, but not ultrasound - Haeberle, Lothar; Hack, Carolin; Heusinger, Katharina; Wagner, Florian; Jud, Sebastian; Uder, Michael; Beckmann, Matthias; Schulz-Wendtland, Rüdiger; Wittenberg, Thomas; Fasching, Peter (European Journal of Medical Research, 2017)
BACKGROUND: Tumors in radiologically dense breast were overlooked on mammograms more often than tumors in low-density breasts. A fast reproducible and automated method of assessing percentage mammographic density (PMD) would be desirable to support decisions whether ultrasonography should be provided for women in addition to mammography in diagnostic mammography units. PMD assessment has still not been included in clinical routine work, as there are issues of interobserver variability and the procedure is quite time consuming. This study investigated whether fully automatically generated texture features of mammograms can replace time-consuming semi-automatic PMD assessment to predict a patient's risk of having an invasive breast tumor that is visible on ultrasound but masked on mammography (mammography failure). METHODS: This observational study included 1334 women with invasive breast cancer treated at a hospital-based diagnostic mammography unit. Ultrasound was available for the entire cohort as part of routine diagnosis. Computer-based threshold PMD assessments ("observed PMD") were carried out and 363 texture features were obtained from each mammogram. Several variable selection and regression techniques (univariate selection, lasso, boosting, random forest) were applied to predict PMD from the texture features. The predicted PMD values were each used as new predictor for masking in logistic regression models together with clinical predictors. These four logistic regression models with predicted PMD were compared among themselves and with a logistic regression model with observed PMD. The most accurate masking prediction was determined by cross-validation. RESULTS: About 120 of the 363 texture features were selected for predicting PMD. Density predictions with boosting were the best substitute for observed PMD to predict masking. Overall, the corresponding logistic regression model performed better (cross-validated AUC, 0.747) than one without mammographic density (0.734), but less well than the one with the observed PMD (0.753). However, in patients with an assigned mammography failure risk >10%, covering about half of all masked tumors, the boosting-based model performed at least as accurately as the original PMD model. CONCLUSION: Automatically generated texture features can replace semi-automatically determined PMD in a prediction model for mammography failure, such that more than 50% of masked tumors could be discovered.
UnivIS-Import:2017-12-18:Pub.2017.tech.IMMD.IMMD9.usinga
Keywords: Mammographic density; Mammography screening; Masking; Risk prediction; Sensitivity; Texture analysis; Variable selection

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

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

Uterus didelphys and cervical cancer: A case report - Krückel, Annika; Saatze, Miriam; Behrens, Annika; Beckmann, Matthias; Pöschke, Patrik; Emons, Julius (Gynecologic Oncology Reports, 2024)
Background: Deficiencies in the merging process of the paramesonephric ducts as part of the embryonal development lead to anomalies of the uterus, cervix, fallopian tubes and proximal vagina (Müllerian malformations). The co-occurrence with cervical cancer is rare and there are no standardized protocols for managing urogenital anomalies in the realm of oncologic treatment for gynecological carcinomas. Case report: A symptom-free 41-year-old woman (gravida 0) presented at our clinic with an externally obtained AGC-FN (atypical glandular cells – favor neoplastic) finding in the Papanicolaou (Pap) smear test and persistent positivity for human papillomavirus (HPV) type 16. Sample biopsies from the portio vaginalis uteri confirmed a cervical intraepithelial neoplasia (CIN) III/ high grade squamous intraepithelial lesion (HSIL), invasive carcinoma could not be ruled out. The examinations revealed the incidental finding of a uterus didelphys and renal agenesis on the left side. After cervical conization, the patient was diagnosed with squamous cell carcinoma of the cervix. Guideline-compliant treatment with laparotomic hysterectomy according to Piver type II following a staging laparoscopy with sentinel lymphadenectomy was performed. A customized protocol was used for the indocyanine green (ICG) injection as part of the sentinel lymph node examination, tailored to the patient's anatomical characteristics. Discussion: Müllerian malformations may impede detection and treatment of gynecological carcinomas. Individualized therapy planning is necessary to meet the anatomical peculiarities of the genital anomaly. In instances of concomitant urinary tract anomalies, protective measures are imperative to safeguard normal kidney function. Conclusion: The current case demonstrates the successful implementation of guideline-compliant therapy for early-stage cervical cancer in an individual with Müllerian malformation.
CRIS-Team Scopus Importer:2024-09-20
Keywords: Cervical cancer; Urogenital anomaly; Uterus didelphys

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

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

Validation and functional follow-up of cervical cancer risk variants at the HLA locus - Eisenblätter, Rieke; Seifert, Finja; Schürmann, Peter; Beckhaus, Theresa; Hanel, Patricia; Jentschke, Matthias; Böhmer, Gerd; Strauß, Hans Georg; Hirchenhain, Christine; Schmidmayr, Monika; Müller, Florian; Hein, Alexander; et al. (HLA, 2024)
Cervical cancer is the fourth most common cancer in females. Genome-wide association studies (GWASs) have proposed cervical cancer susceptibility variants at the HLA locus on chromosome 6p21. To corroborate these findings and investigate their functional impact in cervical tissues and cell lines, we genotyped nine variants from cervical cancer GWASs (rs17190106, rs535777, rs1056429, rs2763979, rs143954678, rs113937848, rs3117027, rs3130214, and rs9477610) in a German hospital-based series of 1122 invasive cervical cancers, 1408 dysplasias, and 1196 healthy controls. rs17190106, rs1056429 and rs143954678/rs113937848 associated with cervical malignancies overall, while rs17190106 and rs535777 associated specifically with invasive cancer (OR = 0.69, 95% CI = 0.55–0.86, p = 0.001) or adenocarcinomas (OR = 1.63, 95%CI = 1.17–2.27, p = 0.004), respectively. We tested these and one previously genotyped GWAS variant, rs9272117, for potential eQTL effects on 36 gene transcripts at the HLA locus in 280 cervical epithelial tissues. The strongest eQTL pairs were rs9272117 and HLA-DRB6 (p = 1.9x10E-5), rs1056429 and HLA-DRB5 (p = 2.5x10E-4), and rs535777 and HLA-DRB1 (p = 2.7x10E-4). We also identified transcripts that were specifically upregulated (DDX39B, HCP5, HLA-B, LTB, NFKBIL1) or downregulated (HLA-C, HLA-DPB2) in HPV+ or HPV16+ samples. In comparison, treating cervical epithelial cells with proinflammatory cytokine γ-IFN led to a dose-dependent induction of HCP5, HLA-B, HLA-C, HLA-DQB1, HLA-DRB1, HLA-DRB6, and repression of HSPA1L. Taken together, these results identify relevant genes from both the MHC class I and II regions that are inflammation-responsive in cervical epithelium and associate with HPV (HCP5, HLA-B, HLA-C) and/or with genomic cervical cancer risk variants (HLA-DRB1, HLA-DRB6). They may thus constitute important contributors to the immune escape of precancerous cells after HPV-infection.
CRIS-Team Scopus Importer:2024-08-16
Keywords: cervical malignancy; eQTL; HPV; IFNG; replication; SNP; susceptibility

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

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

Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility - Earp, Madalene; Tyrer, Jonathan P.; Winham, Stacey J.; Lin, Hui-Yi; Chornokur, Ganna; Dennis, Joe; Aben, Katja K. H.; Anton-Culver, Hoda; Antonenkova, Natalia; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias; et al. (PLoS ONE, 2018)
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
EVALuna2:34624

Variation in NF-?B signaling pathways and survival in invasive epithelial ovarian cancer - Block, Matthew S.; Charbonneau, Bridget; Vierkant, Robert A.; Fogarty, Zachary; Bamlet, William R.; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel; Pearce, Celeste Leigh; Schildkraut, Joellen; Menon, Usha; et al. (Cancer Epidemiology Biomarkers & Prevention, 2014)
Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-?B (NF-?B) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-?B family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10(-5)). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10(-6)] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10(-5)). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 × 10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10(-4)). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.
EVALuna2:9241

Venöse Luftembolie bei vaginalen Verletzungen durch Geschlechtsverkehr - Zack, F.; Zinka, B.; Beckmann, Matthias; Banaschak, Sibylle; Fischer, H.; Gabriel, P.; Gerber, B.; Costa, S. D.; Ledwon, P.; Schwenzer, T.; Buettner, A. (Rechtsmedizin, 2019)
Background: In a criminal trial in Germany in 2013, a medical expert nominated by the defence stated in the appeal trial the controversially discussed opinion that a woman had died from an air embolism due to vaginal intercourse with exclusively penile penetration and injury to the vaginal wall. This diagnosis had been established by the expert based on histological examination of the lungs and vaginal injuries years after the woman‘s death. Objective: The frequency of the diagnosis “air embolism as a result of vaginal injuries due to intravaginal intercourse” and the modality of the diagnosis were reviewed. Material and methods: A selective literature review was performed. Furthermore, questionnaires were sent to all forensic medical institutes and to directors and chief physicians of gynecological clinics of large cities in Germany. Results: In the literature two case reports could be found, which by critical analysis showed significant errors in the diagnosis according to the state of science at the time of publication. In over 300,000 autopsies performed between 1990 and 2016, the 26 forensic medical institutes in Germany, which had answered the questionnaire, had never diagnosed “air embolism as a result of vaginal injuries due to intravaginal intercourse”. All 32 professionally experienced gynecologists who responded to the questionnaire had never in their career treated survived or fatal cases of air embolism after vaginal injuries through sexual intercourse or had knowledge of them. Conclusion: According to the survey and critical analysis of the very few published case reports, there is no evidence for a diagnosis of the cause of death as air embolism after vaginal injuries. When diagnosing a fatal venous air embolism, scientific standards should be strictly followed. A diagnosis made solely by histological examination was and is not possible according to the state of the art in forensic medicine and thus violates the principles of expert medical opinions.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Cause of death; Expert opinion; Pregnancy; Questionnaire; Sexual behavior

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

Ventral rectopexy with biological mesh: short-term functional results - Brunner, Michaela; Roth, H.; Guenther, K.; Grützmann, Robert; Matzel, K. E. (International Journal of Colorectal Disease, 2018)
PURPOSE: Ventral mesh rectopexy (VMR) is an established, minimally invasive, nerve-sparing procedure for the treatment of various symptomatic morphological changes in the posterior pelvic compartment. We present the short-term functional outcome and patient satisfaction after laparoscopic and robotic VMR with biological mesh. METHODS: We analyzed data from 123 patients who underwent laparoscopic ventral mesh rectopexy (LVMR) or robotic ventral mesh rectopexy (RVMR) from August 2012 to January 2017. Included in these data were patient demographics, intra- and postoperative findings, Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), Cleveland Clinic Incontinence Score (CCIS), and patient satisfaction as measured by visual analog scale (0-10). RESULTS: Improvements in CCCS, CCIS, and ODS were statistically significant at 6 and 12 months (p < 0.001). Patient satisfaction was excellent at 6 and 12 months (8.2/10 and 8.3/10, respectively). The overall complication rate was 14%, with a major complication rate of 2%. No mesh-related complications were observed. The need for surgical re-intervention because of relapse, symptom persistence or recurrence, or new symptoms was 3%. Outcome appears to be similar between LVMR and RVMR. CONCLUSIONS: Both LVMR and RVMR with biological mesh are safe and effective in reducing symptoms, as measured by CCCS, CCIS, and ODS, and patient satisfaction is high.
EVALuna2:212626

Veranstaltungsbericht: 10. Wissenschaftliches Symposium der AGO-TraFo - Banys-Paluchowski, Malgorzata; Antoniadis, Sophia; Hein, Alexander; Fehm, Tanja N.; Arnold, Norbert; Fasching, Peter (Geburtshilfe und Frauenheilkunde, 2018)
CRIS-Team Scopus Importer:2021-07-19

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

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

Virilizing Hilus Cell Tumor of the Ovary Associated With Efferent Ductules-like Metaplasia Within Paratubal Mesonephric Remnants - Wachter, David; Burghaus, Stefanie; Beckmann, Matthias; Agaimy, Abbas (International Journal of Gynecological Pathology, 2016)
EVALuna2:6767

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

WebPPG: Feasibility and Usability of Self-Performed, Browser-Based Smartphone Photoplethysmography - Nissen, Michael; Flaucher, Madeleine; Jäger, Katharina; Hübner, Hanna; Danzberger, Nina; Titzmann, Adriana; Pontones, Constanza; Fasching, Peter; Eskofier, Björn; Leutheuser, Heike (2023 45th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), 2023)
Smartphones enable and facilitate biomedical studies as they allow the recording of various biomedical signals, including photoplethysmograms (PPG). However, user engagement rates in mobile health studies are reduced when an application (app) needs to be installed. This could be alleviated by using installation-free web apps. We evaluate the feasibility of browser-based PPG recording, conducting the first usability study on smartphone-based PPG. We present an at-home study using a web app and library for PPG recording using the rear camera and flash. The underlying library is freely made available to researchers. 25 Android users participated, using their own smartphones. The study consisted of a demographic and anamnestic questionnaire, the signal recording itself (60 s), and a consecutive usability questionnaire. After filtering, heart rate was extracted (14/17 successful), signal-to-noise ratios assessed (0.64 ± 0.50 dB, mean ± standard deviation), and quality was visually inspected (12/17 usable for diagnosis). Recording was not supported in 9 cases. This was due to the browser's insufficient support for the flash light API. The app received a System Usability Scale score of 82 ± 9, which is above the 90th percentile. Overall, browser flash light support is the main limiting factor for broad device support. Thus, browser-based PPG is not yet widely applicable, although most participants feel comfortable with the recording itself. The utilization of the user-facing camera might represent a more promising approach. This study contributes to the development of low-barrier, user-friendly, installation-free smartphone signal acquisition. This enables profound, comprehensive data collection for research and clinical practice.Clinical relevance - WebPPG offers low-barrier remote diagnostic capabilities without the need for app installation
Created from Fastlane, Scopus look-up
Keywords: Heart rate; Limiting; Cameras; Photoplethysmography; Libraries; Recording; Usability

What do patients want to know about contraception and which method would they prefer? - Oppelt, Patricia; Baier, Friederike; Fahlbusch, Christine; Heusinger, Katharina; Hildebrandt, Thomas; Breuel, Christiane; Dittrich, Ralf (Archives of Gynecology and Obstetrics, 2017)
PURPOSE: The aim of this study was to determine the extent to which women's choice of contraceptive method depends on the advice received from their gynecologist and whether more intensive counseling might lead to more frequent use of long-acting reversible contraception (LARC). METHODS: A total of 1089 physicians and 18,521 women responded to 32 or 37 questions, respectively, using an online questionnaire. The women were asked about their current use of contraceptive methods, the extent of their satisfaction with them, their satisfaction with the counseling they had received, and whether they wanted to have more information about contraception. The physicians were similarly asked which contraceptive methods were being used, how satisfied with them they were, how they would assess their patients' satisfaction with them, and whether the women wanted to have more information. RESULT: The results showed that 61% of the women were using oral contraceptives, and a total of only 9% were using behavior-independent long-term contraceptive methods. However, 60% of the women stated that long-term contraception would be an option for them if they had more information about it. Gynecologists underestimated this figure, at only 18%. Whereas 66% of the gynecologists believed that their patients never forgot to take the pill, nearly, half of the women stated that they had forgotten it at least once during the previous 3 months. CONCLUSION: The small number of women who use long-term contraception is in clear contrast to the fact that many women want to have a very safe but also behavior-independent method.
EVALuna2:36175

Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients - Alunni-Fabbroni, Marianna; Majunke, Leonie; Trapp, Elisabeth K.; Tzschaschel, Marie; Mahner, Sven; Fasching, Peter; Fehm, Tanja; Schneeweiss, Andreas; Beck, Thomas; Lorenz, Ralf; Friedl, Thomas W. P.; Janni, Wolfgang; et al. (BMC Cancer, 2018)
microRNAs (miRNAs) are considered promising cancer biomarkers, showing high reliability, sensitivity and stability. Our study aimed to identify associations between whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-operative early breast cancer patients (EBC) to assess the utility of miRNAs as prognostic markers in this setting.A total of 48 post-operative patients, recruited in frame of the SUCCESS A trial, were included in this retrospective study and tested with a panel of 8 miRNAs (miR-10b, -19a, - 21, - 22, -20a, - 127, - 155, -200b). Additional 17 female healthy donors with no previous history of cancer were included in the study as negative controls. Blood samples were collected at different time points (pre-adjuvant therapy, post-adjuvant therapy, 2 years follow up), total RNA was extracted and the relative concentration of each miRNA was measured by quantitative PCR and compared in patients stratified on blood collection time or CTC detection. Furthermore, we compared miRNA profiles of patients, for each time point separately, and healthy donors. CTCs were visualized and quantified with immunocytochemistry analysis. Data were analyzed using non-parametric statistical tests.In our experimental system, miR-19a, miR-22 and miR-127 showed the most promising results, differentiating patients at different time points and from healthy controls, while miR-20a, miR-21 and miR-200b did not show any difference among the different groups. miR-10b and miR-155 were never detectable in our experimental system. With respect to patients' clinical characteristics, we found a significant correlation between miR-200b and lymph node status and between miR-20a and tumor type. Furthermore, miR-127 correlated with the presence of CTCs. Finally, we found a borderline significance between Progression Free Survival and miR-19a levels.This pilot study suggests that profiling whole blood miRNAs could help to better stratify post-operative EBC patients without any sign of metastasis to prevent later relapse or metastatic events.
EVALuna2:56167

Whole-Body Electromyostimulation combined with personalized Nutritional Support improves the Body Composition of Patients with advanced Cancer - Schink, Kristin; Herrmann, Hans Joachim; Schwappacher, Raphaela; Orlemann, Till; Meyer, Julia; Waldmann, Elisabeth; Wullich, Bernd; Kahlmeyer, Andreas; Fietkau, Rainer; Lubgan, Dorota; Beckmann, Matthias; Hack, Carolin; et al. (2018)
EVALuna2:35187

Willingness of Patients with Breast Cancer in the Adjuvant and Metastatic Setting to Use Electronic Surveys (ePRO) Depends on Sociodemographic Factors, Health-related Quality of Life, Disease Status and Computer Skills - Graf, Joachim; Simoes, E.; Wisslicen, K.; Rava, L.; Walter, C. B.; Hartkopf, A.; Keilmann, L.; Taran, A.; Wallwiener, S.; Fasching, Peter; Brucker, S. Y.; Wallwiener, M. (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: Because of the often unfavorable prognosis, particularly for patients with metastases, health-related quality of life is extremely important for breast cancer patients. In recent years, data on patient-relevant endpoints is being increasingly collected electronically; however, knowledge on the acceptance and practicability of, and barriers to, this form of data collection remains limited.Material and Methods:A questionnaire was completed by 96 patients to determine to what extent existing computer skills, disease status, health-related quality of life and sociodemographic factors affect patients' potential willingness to use electronics methods of data collection (ePRO).Results:52 of 96 (55 %) patients reported a priori that they could envisage using ePRO. Patients who a priori preferred a paper-based survey (pPRO) tended to be older (ePRO 53 years vs. pPRO 62 years; p = 0.0014) and typically had lower levels of education (p = 0.0002), were in poorer health (p = 0.0327) and had fewer computer skills (p = 0.0003).Conclusion:Barriers to the prospective use of ePRO were identified in older patients and patients with a lower quality of life. Given the appropriate conditions with regard to age, education and current health status, opportunities to participate should be provided to encourage patients' willingness to take part and ensure the validity of survey results. Focusing on ease of use of ePRO applications and making applications more patient-oriented and straightforward appears to be the way forward.
EVALuna2:33539

Xenotransplantation of cryopreserved human ovarian tissue - a systematic review of MII oocyte maturation and discussion of it as a realistic option for restoring fertility after cancer treatment - Dittrich, Ralf; Lotz, Laura; Fehm, Tanja; Kruessel, Jan; Von Wolff, Michael; Toth, Bettina; Van Der Ven, Hans; Schuering, Andreas N.; Wuerfel, Wolfgang; Hoffmann, Inge; Beckmann, Matthias (Fertility and Sterility, 2015)
To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue.Systematic review in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).Not applicable.Not applicable.Formation of MII oocytes after xenotransplantation of human ovarian tissue.Any outcome reported in Pubmed.Six publications were identified that report on formation of MII oocytes after xenotransplantation of human ovarian tissue.Xenografting of human ovarian tissue has proved to be a useful model for examining ovarian function and follicle development in vivo. With human follicles that have matured through xenografting, the possibility of cancer transmission and relapse can also be eliminated, because cancer cells are not able to penetrate the zona pellucida. The reported studies have demonstrated that xenografted ovarian tissue from a range of species, including humans, can produce antral follicles that contain mature (MII) oocytes, and it has been shown that mice oocytes have the potential to give rise to live young. Although some ethical questions remain unresolved, xenotransplantation may be a promising method for restoring fertility. This review furthermore describes the value of xenotransplantation as a tool in reproductive biology and discusses the ethical and potential safety issues regarding ovarian tissue xenotransplantation as a means of recovering fertility.
EVALuna2:17543

Zoledronate for patients with invasive residual disease after anthracyclines-taxane-based chemotherapy for early breast cancer - The Phase III NeoAdjuvant Trial Add-oN (NaTaN) study (GBG 36/ABCSG 29) - Von Minckwitz, G.; Rezai, M.; Tesch, H.; Huober, J.; Gerber, B.; Zahm, D. M.; Hilfrich, J.; Costa, S. D.; Dubsky, P.; Blohmer, J. U.; Denkert, Carsten; Hanusch, C.; et al. (European Journal of Cancer, 2016)
BACKGROUND: Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. PATIENTS AND METHODS: Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. RESULTS: After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified. CONCLUSION: Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.
EVALuna2:33068

Zukunft mammographie-basierter Bildgebung [Future of mammography-based imaging] - Schulz-Wendtland, Rüdiger; Wittenberg, Thomas; Michel, Thilo; Hartmann, Arndt; Beckmann, Matthias; Rauh, Claudia; Judt, Sebastian; Brehm, Barbara; Meier-Meitinger, Martina; Anton, Gisela; Uder, Michael; Fasching, Peter (Radiologe, 2014)
Mammography is the central diagnostic method for clinical diagnostics of breast cancer and the breast cancer screening program. In the clinical routine complementary methods, such as ultrasound, tomosynthesis and optional magnetic resonance imaging (MRI) are already combined for the diagnostic procedure. Future developments will utilize investigative procedures either as a hybrid (combination of several different imaging modalities in one instrument) or as a fusion method (the technical fusion of two or more of these methods) to implement fusion imaging into diagnostic algorithms. For screening there are reasonable hypotheses to aim for studies that individualize the diagnostic process within the screening procedure. Individual breast cancer risk prediction and individualized knowledge about sensitivity and specificity for certain diagnostic methods could be tested. The clinical implementation of these algorithms is not yet in sight. (orig.) [German] Die Mammographie ist die zentrale diagnostische Methode der klinischen symptombezogenen Abklaerung von Brusterkrankungen und des Brustkrebsscreenings. In der klinischen Diagnostik wird sie heute schon oft durch zusaetzliche Untersuchungsmethoden wie dem Ultraschall, der Tomosynthese und ggf. auch der MRT-Bildgebung unterstuetzt. Zukuenftige Entwicklungen gehen in die Richtung, dass diese Kombination aus 2 oder mehr Untersuchungsverfahren entweder in Hybrid- (Aufnahme mehrerer unterschiedlicher Bildmodalitaeten in einem einzigen Geraet) oder in Fusionsmethoden (Zusammenfuehrung und Registrierung von Bilddaten aus verschiedenen Modalitaeten) technisch professionalisiert werden. Des Weiteren koennten an subgruppenbezogene Erkrankungsrisiken und individuelle Sensitivitaeten und Spezifitaeten angepasste Diagnostikkombinationen fuer eine Screeningdiagnostik Gegenstand kuenftiger Studien sein. Wir stellen die aktuellen Entwicklungen auf diesen Gebieten und deren momentane Relevanz fuer die klinische Praxis und Entwicklungspotenzial fuer die Zukunft dar. (orig
UnivIS-Import:2015-04-14:Pub.2014.tech.IMMD.IMMD9.zukunf
Keywords: MAMMOgraphy

Complementary medicine in radiation oncology : German health care professionals' current qualifications and therapeutic methods - Kessel, Kerstin A.; Klein, Evelyn; Hack, Carolin; Combs, Stephanie E. (Strahlentherapie und Onkologie, 2018)
Recently, complementary and alternative medicine (CAM) has moved more into the focus, and cancer societies such as the German Cancer Society (Deutsche Krebsgesellschaft, DKG) have established working groups to develop a guideline for CAM. The present work aims to evaluate the acceptance of CAM in the whole radiation oncology community.We conducted an online survey on CAM and sent the modified questionnaire that was successfully distributed to all members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynakologische Onkologie, AGO) of the DKG in 2014 to the members of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie und Strahlentherapie, DEGRO). The survey consisted of 17 questions regarding personal information and current CAM guidelines within the workplace/clinic.A total of 143 members participated. Of these, 12% had some CAM qualification. For hematological cancer in 35% and in up to 76% for breast cancer, CAM treatment is offered in German radiation oncology facilities, mainly due to fatigue symptoms. CAM is part of routine treatment in 32.2%, 22.0% are planning to incorporate it. Most physicians advise patients to partake in sports activities and recommend dietary supplements and nutritional counseling. The cost of CAM treatment is fully covered in 9.8% of all participating facilities.Today, CAM is integrated into cancer care; however, skepticism regarding its effect still exists. Evidence-based results must be generated to convince physicians of the effectiveness of CAM methods. CAM qualifications must be included in physicians' training to improve their understanding and counseling regarding CAM options in cancer care.
EVALuna2:92076

Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden - Stone, Meredith L.; Chiappinelli, Katherine B.; Li, Huili; Murphy, Lauren M.; Travers, Meghan E.; Topper, Michael J.; Mathios, Dimitrios; Lim, Michael; Shih, Ie-Ming; Wang, Tian-Li; Hung, Chien-Fu; Bhargava, Vipul; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2017)
Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy. These data indicate that the type I IFN response is required for effective in vivo antitumorigenic actions of the DNMTi 5-azacytidine (AZA). Through type I IFN signaling, AZA increases the numbers of CD45+ immune cells and the percentage of active CD8+ T and natural killer (NK) cells in the tumor microenvironment, while reducing tumor burden and extending survival. AZA also increases viral defense gene expression in both tumor and immune cells, and reduces the percentage of macrophages and myeloid-derived suppressor cells in the tumor microenvironment. The addition of an HDACi to AZA enhances the modulation of the immune microenvironment, specifically increasing T and NK cell activation and reducing macrophages over AZA treatment alone, while further increasing the survival of the mice. Finally, a triple combination of DNMTi/HDACi plus the immune checkpoint inhibitor α-PD-1 provides the best antitumor effect and longest overall survival, and may be an attractive candidate for future clinical trials in ovarian cancer.
EVALuna2:36339

Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer - Topper, Michael J.; Vaz, Michelle; Chiappinelli, Katherine B.; Shields, Christina E. Destefano; Niknafs, Noushin; Yen, Ray-Whay Chiu; Wenzel, Alyssa; Hicks, Jessica; Ballew, Matthew; Stone, Meredith; Tran, Phuoc T.; Zahnow, Cynthia A.; et al. (Cell, 2017)
Combining DNA-demethylating agents (DNA methyltransferase inhibitors [DNMTis]) with histone deacetylase inhibitors (HDACis) holds promise for enhancing cancer immune therapy. Herein, pharmacologic and isoform specificity of HDACis are investigated to guide their addition to a DNMTi, thus devising a new, low-dose, sequential regimen that imparts a robust anti-tumor effect for non-small-cell lung cancer (NSCLC). Using in-vitro-treated NSCLC cell lines, we elucidate an interferon α/β-based transcriptional program with accompanying upregulation of antigen presentation machinery, mediated in part through double-stranded RNA (dsRNA) induction. This is accompanied by suppression of MYC signaling and an increase in the T cell chemoattractant CCL5. Use of this combination treatment schema in mouse models of NSCLC reverses tumor immune evasion and modulates T cell exhaustion state towards memory and effector T cell phenotypes. Key correlative science metrics emerge for an upcoming clinical trial, testing enhancement of immune checkpoint therapy for NSCLC.
EVALuna2:36340

MicroRNA-mediated drug resistance in ovarian cancer - Mihanfar, Aynaz; Fattahi, Amir; Nejabati, Hamid Reza (Journal of Cellular Physiology, 2019)
The development of intrinsic or acquired resistance to chemotherapeutic agents used in the treatment of various human cancers is a major obstacle for the successful abolishment of cancer. The accumulated efforts in the understanding the exact mechanisms of development of multidrug resistance (MDR) have led to the introduction of several unique and common mechanisms. Recent studies demonstrate the regulatory role of small noncoding RNA or miRNA in the several parts of cancer biology. Practically all aspects of cell physiology under normal and disease conditions are reported to be controlled by miRNAs. In this review, we discuss how the miRNA profile is changed upon MDR development and the pivotal regulatory role played by miRNAs in overcoming resistance to chemotherapeutic agents. It is hoped that further studies will support the use of these differentially expressed miRNAs as prognostic and predictive markers, as well as novel therapeutic targets to overcome resistance in ovarian cancer.
CRIS-Team WoS Importer:2019-02-22

Reply to Haffner et al.: DNA hypomethylation renders tumors more immunogenic - Stone, Meredith L.; Chiappinelli, Katherine B.; Li, Huili; Murphy, Lauren M.; Travers, Meghan E.; Topper, Michael J.; Mathios, Dimitrios; Lim, Michael; Shih, Le-Ming; Wang, Tian-Li; Hung, Chien-Fu; Bhargava, Vipul; et al. (Proceedings of the National Academy of Sciences of the United States of America, 2018)
EVALuna2:210063

Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study - Woelber, Linn; Griebel, Lis-Femke; Eulenburg, Christine; Sehouli, Jalid; Jueckstock, Julia; Hilpert, Felix; De Gregorio, Nikolaus; Hasenburg, Annette; Ignatov, Atanas; Hillemanns, Peter; Fuerst, Sophie; Strauss, Hans-Georg; et al. (European Journal of Cancer, 2016)
AIM OF THE STUDY: A tumour-free pathological resection margin of ≥8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer. METHODS: AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer ≥ FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289). RESULTS: Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin <8 mm and 10.2% in patients with a margin ≥8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p = 0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267). CONCLUSIONS: The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database.
EVALuna2:33467

Unraveling the molecular pathways of DNA-methylation inhibitors: human endogenous retroviruses induce the innate immune response in tumors - Strick, Reiner; Strissel, Pamela; Baylin, Stephen B.; Chiappinelli, Katherine B. (OncoImmunology, 2016)
Loss of DNA methylation can activate endogenous retroviral expression and dsRNA in cancer cells. This leads to induction of toll-like receptor signaling stimulating an antiviral interferon response. Recent findings provide a therapeutic rationale for combining DNA methylation inhibitors with blockage of immune checkpoint proteins to fight cancer.
EVALuna2:33459