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La generación de nuevos materiales genéticos para atender las diversas demandas del mercado de la madera requiere una constante evaluación de sus propiedades tecnológicas. En el presente estudio, se evaluó el contenido relativo de duramen y albura a tres alturas de fuste (0,10 m, 2,80 m y 5,50 m) así como la variación de densidad en dirección axial y radial de clones puros Eucalyptus grandis (rose gum) e híbridos (Eucalyptus grandis (rose gum) x Eucalyptus camaldulensis (red gum) y Eucalyptus grandis (rose gum) x Eucalyptus tereticornis (red irongum)) de 11 años de edad. Los clones puros mostraron un 10 % más de duramen que los híbridos. El material híbrido alcanzó el mayor valor medio de densidades, siendo más homogéneo en el perfil radial y axial. En general, la densidad presentó un patrón creciente en la dirección radial. No se encontraron diferencias significativas en la densidad para las alturas estudiadas en los clones híbridos, mientras que los clones puros presentaron valores de densidad significativamente mayores a 0,10 m. La densidad de la albura fue mayor que la del duramen para las tres alturas de fuste en todos los materiales genéticos. El análisis de los resultados indica que los clones híbridos podrían ser aptos para la producción de pulpa de celulosa debido a la menor proporción de duramen, lo cual facilita el proceso de blanqueo, así como para su uso como madera aserrada o contrachapado estructural por su mayor densidad y homogeneidad en altura, La generación de nuevos materiales genéticos para atender las diversas demandas del mercado de la madera requiere una constante evaluación de sus propiedades tecnológicas. En el presente estudio, se evaluó el contenido relativo de duramen y albura a tres alturas de fuste (0,10 m, 2,80 m y 5,50 m) así como la variación de densidad en dirección axial y radial de clones puros Eucalyptus grandis (rose gum) e híbridos (Eucalyptus grandis (rose gum) x Eucalyptus camaldulensis (red gum) y Eucalyptus grandis (rose gum) x Eucalyptus tereticornis (red irongum)) de 11 años de edad. Los clones puros mostraron un 10 % más de duramen que los híbridos. El material híbrido alcanzó el mayor valor medio de densidades, siendo más homogéneo en el perfil radial y axial. En general, la densidad presentó un patrón creciente en la dirección radial. No se encontraron diferencias significativas en la densidad para las alturas estudiadas en los clones híbridos, mientras que los clones puros presentaron valores de densidad significativamente mayores a 0,10 m. La densidad de la albura fue mayor que la del duramen para las tres alturas de fuste en todos los materiales genéticos. El análisis de los resultados indica que los clones híbridos podrían ser aptos para la producción de pulpa de celulosa debido a la menor proporción de duramen, lo cual facilita el proceso de blanqueo, así como para su uso como madera aserrada o contrachapado estructural por su mayor densidad y homogeneidad en altura.

La generación de nuevos materiales genéticos para atender las diversas demandas del mercado de la madera requiere una constante evaluación de sus propiedades tecnológicas. En el presente estudio, se evaluó el contenido relativo de duramen y albura a tres alturas de fuste (0,10 m, 2,80 m y 5,50 m) así como la variación de densidad en dirección axial y radial de clones puros Eucalyptus grandis (rose gum) e híbridos (Eucalyptus grandis (rose gum) x Eucalyptus camaldulensis (red gum) y Eucalyptus grandis (rose gum) x Eucalyptus tereticornis (red irongum)) de 11 años de edad. Los clones puros mostraron un 10 % más de duramen que los híbridos. El material híbrido alcanzó el mayor valor medio de densidades, siendo más homogéneo en el perfil radial y axial. En general, la densidad presentó un patrón creciente en la dirección radial. No se encontraron diferencias significativas en la densidad para las alturas estudiadas en los clones híbridos, mientras que los clones puros presentaron valores de densidad significativamente mayores a 0,10 m. La densidad de la albura fue mayor que la del duramen para las tres alturas de fuste en todos los materiales genéticos. El análisis de los resultados indica que los clones híbridos podrían ser aptos para la producción de pulpa de celulosa debido a la menor proporción de duramen, lo cual facilita el proceso de blanqueo, así como para su uso como madera aserrada o contrachapado estructural por su mayor densidad y homogeneidad en altura, La generación de nuevos materiales genéticos para atender las diversas demandas del mercado de la madera requiere una constante evaluación de sus propiedades tecnológicas. En el presente estudio, se evaluó el contenido relativo de duramen y albura a tres alturas de fuste (0,10 m, 2,80 m y 5,50 m) así como la variación de densidad en dirección axial y radial de clones puros Eucalyptus grandis (rose gum) e híbridos (Eucalyptus grandis (rose gum) x Eucalyptus camaldulensis (red gum) y Eucalyptus grandis (rose gum) x Eucalyptus tereticornis (red irongum)) de 11 años de edad. Los clones puros mostraron un 10 % más de duramen que los híbridos. El material híbrido alcanzó el mayor valor medio de densidades, siendo más homogéneo en el perfil radial y axial. En general, la densidad presentó un patrón creciente en la dirección radial. No se encontraron diferencias significativas en la densidad para las alturas estudiadas en los clones híbridos, mientras que los clones puros presentaron valores de densidad significativamente mayores a 0,10 m. La densidad de la albura fue mayor que la del duramen para las tres alturas de fuste en todos los materiales genéticos. El análisis de los resultados indica que los clones híbridos podrían ser aptos para la producción de pulpa de celulosa debido a la menor proporción de duramen, lo cual facilita el proceso de blanqueo, así como para su uso como madera aserrada o contrachapado estructural por su mayor densidad y homogeneidad en altura.

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

With abemaciclib (monarchE study) and olaparib (OlympiA study) gaining approval in the adjuvant treatment setting, a significant change in the standard of care for patients with early stage breast cancer has been established for some time now. Accordingly, some diverse developments are slowly being transferred from the metastatic to the adjuvant treatment setting. Recently, there have also been positive reports of the NATALEE study.Other clinical studies are currently investigating substances that are already established in the metastatic setting. These include, for example, the DESTINY Breast05 study with trastuzumab deruxtecan and the SASCIA study with sacituzumab govitecan.In this review paper, we summarize and place in context the latest developments over the past months.

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.

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.

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023. Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

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.

The St. Gallen (SG) International Breast Cancer Conference is held every two years, previously in St. Gallen and now in Vienna. This year (2023) marks the eighteenth edition of this conference, which focuses on the treatment of patients with early-stage breast carcinoma. A panel discussion will be held at the end of this four-day event, during which a panel of experts will give their opinions on current controversial issues relating to the treatment of early-stage breast cancer patients. To this end, questions are generally formulated in such a way that clinically realistic cases are presented – often including poignant hypothetical modifications. This review reports on the outcome of these discussions and summarises the data associated with individual questions raised.

One of the most significant climate changes in the history of Earth happened during the late Palaeozoic, with the melting of the Gondwanan ice sheets and a progressive warming that profoundly changed the composition of the global terrestrial biota. Nevertheless, there is a lack of studies on mid-late Cisuralian central Pangaea (presentday Europe and North Africa). We have comprehensively revised the well-constrained tetrapod ichnofauna, macroflora, and microflora from the late Cisuralian of the Southern Alps and compared it to other Cisuralian assemblages from Europe and North Africa. The results show a dramatic increase in both diversity and relative abundance of drought-tolerant forms during the Artinskian, at about 287 Ma. This biotic replacement is sudden, conspicuous, widespread and time-equivalent to the biotic replacement observed at the low palaeolatitudes of western Pangaea (present-day western USA) and to a major increase of pCO2 and Na2O values in Euramerican successions. This is possibly related to the eruption of the Tarim Large Igneous Province of NW China and Panjal Traps of NW India that may have caused the final melting of the Gondwanan ice sheets. Consequently, this substantial faunal and floral change is probably driven by a global climatic event (Artinskian Warming Event, AWE) that increased temperature and aridity at the low palaeolatitudes of Pangaea, enhancing the apparent abundance and diversity of drought-tolerant taxa. Further studies are needed to better constrain the timing of this event and verify its full extent, in both the continental and marine realms, as well as to investigate its relationship with contemporary eruptions.

Background Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women. Methods In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels. Results All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, eta(2)(p) = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, eta(2)(p) = .128. Conclusion Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxa

Background Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women. Methods In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels. Results All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, eta(2)(p) = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, eta(2)(p) = .128. Conclusion Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxa

Background Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women. Methods In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels. Results All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, eta(2)(p) = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, eta(2)(p) = .128. Conclusion Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxa

Background Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women. Methods In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels. Results All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, eta(2)(p) = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, eta(2)(p) = .128. Conclusion Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxa

Background Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women. Methods In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels. Results All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, eta(2)(p) = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, eta(2)(p) = .128. Conclusion Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxa

BackgroundPTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.MethodsTumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.ResultsDownregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016).ConclusionsPTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

This thesis comprises three self-contained essays on the modeling and prediction of realized covariance matrices of asset returns using state-space models.

We propose a dynamic factor state-space model for high-dimensional covariance matrices of asset returns. It makes use of observed risk factors and assumes that the latent integrated joint covariance matrix of the assets and the factors is observed through their realized covariance matrix with a Wishart measurement density. For the latent integrated covariance matrix of the assets we impose a strict factor structure allowing for dynamic variation in the covariance matrices of the factors and the residual components as well as in the factor loadings. This factor structure translates into a factorization of the Wishart measurement density which facilitates statistical inference based on simple Bayesian MCMC procedures making the approach scalable w.r.t. the number of assets. An empirical application to realized covariance matrices for 60 NYSE traded stocks using the Fama-French factors and sector-specific factors represented by Exchange Traded Funds (ETFs) shows that the model performs very well in- and out of sample.

Background: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. Patients and methods: The multicenter phase IV PreFace study evaluated letrozole therapy in post-menopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. Results: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. Conclusions: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients. (C) 2020 The Author(s). Published by Elsevier Ltd.

BACKGROUND: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. METHODS: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests. RESULTS: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). CONCLUSIONS: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

BackgroundPTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.MethodsTumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.ResultsDownregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016).ConclusionsPTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.

This thesis comprises three self-contained essays on the modeling and prediction of realized covariance matrices of asset returns using state-space models.

We propose a dynamic factor state-space model for high-dimensional covariance matrices of asset returns. It makes use of observed risk factors and assumes that the latent integrated joint covariance matrix of the assets and the factors is observed through their realized covariance matrix with a Wishart measurement density. For the latent integrated covariance matrix of the assets we impose a strict factor structure allowing for dynamic variation in the covariance matrices of the factors and the residual components as well as in the factor loadings. This factor structure translates into a factorization of the Wishart measurement density which facilitates statistical inference based on simple Bayesian MCMC procedures making the approach scalable w.r.t. the number of assets. An empirical application to realized covariance matrices for 60 NYSE traded stocks using the Fama-French factors and sector-specific factors represented by Exchange Traded Funds (ETFs) shows that the model performs very well in- and out of sample.

Background: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. Patients and methods: The multicenter phase IV PreFace study evaluated letrozole therapy in post-menopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. Results: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. Conclusions: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients. (C) 2020 The Author(s). Published by Elsevier Ltd.

Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry. Methods:Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria. Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based o

The study of bacterial symbioses has grown exponentially in the recent past. However, existing bioinformatic workflows of microbiome data analysis do commonly not integrate multiple meta-omics levels and are mainly geared toward human microbiomes. Microbiota are better understood when analyzed in their biological context; that is together with their host or environment. Nevertheless, this is a limitation when studying non-model organisms mainly due to the lack of well-annotated sequence references. Here, we present gNOMO, a bioinformatic pipeline that is specifically designed to process and analyze non-model organism samples of up to three meta-omics levels: metagenomics, metatranscriptomics and metaproteomics in an integrative manner. The pipeline has been developed using the workflow management framework Snakemake in order to obtain an automated and reproducible pipeline. Using experimental datasets of the German cockroach Blattella germanica, a non-model organism with very complex gut microbiome, we show the capabilities of gNOMO with regard to meta-omics data integration, expression ratio comparison, taxonomic and functional analysis as well as intuitive output visualization. In conclusion, gNOMO is a bioinformatic pipeline that can easily be configured, for integrating and analyzing multiple meta-omics data types and for producing output visualizations, specifically designed for integrating paired-end sequencing data with mass spectrometry from non-model organisms.

PurposeEvidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients.MethodsThe prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test.ResultsIn a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively).ConclusionsThis analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.

Background Inherited pathogenic variants in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer (HBOC). The risk of developing breast cancer by age 80 in women carrying a BRCA1 pathogenic variant is 72%. The lifetime risk varies between families and even within affected individuals of the same family. The cause of this variability is largely unknown, but it is hypothesized that additional genetic factors contribute to differences in age at onset (AAO). Here we investigated whether truncating and rare missense variants in genes of different DNA-repair pathways contribute to this phenomenon. Methods We used extreme phenotype sampling to recruit 133 BRCA1-positive patients with either early breast cancer onset, below 35 (early AAO cohort) or cancer-free by age 60 (controls). Next Generation Sequencing (NGS) was used to screen for variants in 311 genes involved in different DNA-repair pathways. Results Patients with an early AAO (73 women) had developed breast cancer at a median age of 27 years (interquartile range (IQR); 25.00-27.00 years). A total of 3703 variants were detected in all patients and 43 of those (1.2%) were truncating variants. The truncating variants were found in 26 women of the early AAO group (35.6%; 95%-CI 24.7 - 47.7%) compared to 16 women of controls (26.7%; 95%-CI 16.1 to 39.7%). When adjusted for environmental factors and family history, the odds ratio indicated an increased breast cancer risk for those carrying an additional truncating DNA-repair variant to BRCA1 mutation (OR: 3.1; 95%-CI 0.92 to 11.5; p-value = 0.07), although it did not reach the conventionally acceptable significance level of 0.05. Conclusions To our knowledge this is the first time that the combined effect of truncating variants in DNA-repair genes on AAO in patients with hereditary breast cancer is investigated. Our results indicate that co-occurring truncating variants might be associated with an earlier onset of breast cancer in BRCA1-posit

BackgroundTreatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients.MethodsEvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT.ResultsOut of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment.ConclusionsDespite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process.Trial registrationClinical Trials Number: CFEM345DDE19

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.

In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between efficacy and PD-L1 expression was found in a neoadjuvant study that included pembrolizumab in TNBC. The pathological complete response rate (pCR) was higher in both patient groups with and without PD-L1 expression when pembrolizumab was added to chemotherapy. Another future question is the identification of further patient groups in which efficacy of PARP inhibitors is seen, which are licensed for the pBRCA1/2 germline mutation. These include, for example, patients with mutations in other genes, which are involved in homologous recombination, or patients with tumours that show an abnormality in global tests of homologous recombination deficiencies (HRD tests). The question of whether a PARP inhibitor can be given and with which chemotherapy combination partners is currently being investigated in both breast and ovarian cancer. While the data on improved overall survival are being consolidated for the CDK4/6 inhibitors, knowledge of molecular changes during the therapy and during progression on the therapy is growing. Both the accumulation of PI3K mutations and also PTEN changes might play a part in planning subsequent therapies. This review article summarises these recent developments in breast cancer and in part also in ovarian cancer.

PurposeEvidence shows that genetic and non-genetic risk factors for breast cancer (BC) differ relative to the molecular subtype. This analysis aimed to investigate associations between epidemiological risk factors and immunohistochemical subtypes in a cohort of postmenopausal, hormone receptor-positive BC patients.MethodsThe prospective, single-arm, multicenter phase IV PreFace study (Evaluation of Predictive Factors Regarding the Effectivity of Aromatase Inhibitor Therapy) included 3529 postmenopausal patients with hormone receptor-positive early BC. Data on their epidemiological risk factors were obtained from patients' diaries and their medical histories. Data on estrogen receptor, progesterone receptor, and HER2 receptor status were obtained from pathology reports. Patients with incomplete information were excluded. Data were analyzed using conditional inference regression analysis, analysis of variance, and the chi-squared test.ResultsIn a cohort of 3392 patients, the strongest association with the molecular subtypes of BC was found for hormone replacement therapy (HRT) before diagnosis of early BC. The analysis showed that patients who took HRT at diagnosis had luminal A-like BC more often (83.7%) than those who had never taken HRT or had stopped taking it (75.5%). Luminal B-like BC and HER2-positive BC were diagnosed more often in women who had never taken HRT or had stopped taking it (13.3% and 11.2%, respectively) than in women who were taking HRT at diagnosis of BC (8.3% and 8.0%, respectively).ConclusionsThis analysis shows an association between HRT and the distribution of molecular subtypes of BC. However, no associations between other factors (e.g., age at diagnosis, body mass index, smoking status, age at menopause, number of deliveries, age at first delivery, breastfeeding history, or family history) were noted.

Background Inherited pathogenic variants in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer (HBOC). The risk of developing breast cancer by age 80 in women carrying a BRCA1 pathogenic variant is 72%. The lifetime risk varies between families and even within affected individuals of the same family. The cause of this variability is largely unknown, but it is hypothesized that additional genetic factors contribute to differences in age at onset (AAO). Here we investigated whether truncating and rare missense variants in genes of different DNA-repair pathways contribute to this phenomenon. Methods We used extreme phenotype sampling to recruit 133 BRCA1-positive patients with either early breast cancer onset, below 35 (early AAO cohort) or cancer-free by age 60 (controls). Next Generation Sequencing (NGS) was used to screen for variants in 311 genes involved in different DNA-repair pathways. Results Patients with an early AAO (73 women) had developed breast cancer at a median age of 27 years (interquartile range (IQR); 25.00-27.00 years). A total of 3703 variants were detected in all patients and 43 of those (1.2%) were truncating variants. The truncating variants were found in 26 women of the early AAO group (35.6%; 95%-CI 24.7 - 47.7%) compared to 16 women of controls (26.7%; 95%-CI 16.1 to 39.7%). When adjusted for environmental factors and family history, the odds ratio indicated an increased breast cancer risk for those carrying an additional truncating DNA-repair variant to BRCA1 mutation (OR: 3.1; 95%-CI 0.92 to 11.5; p-value = 0.07), although it did not reach the conventionally acceptable significance level of 0.05. Conclusions To our knowledge this is the first time that the combined effect of truncating variants in DNA-repair genes on AAO in patients with hereditary breast cancer is investigated. Our results indicate that co-occurring truncating variants might be associated with an earlier onset of breast cancer in BRCA1-posit

BackgroundTreatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients.MethodsEvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT.ResultsOut of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment.ConclusionsDespite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process.Trial registrationClinical Trials Number: CFEM345DDE19

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.

In der Prävention und Behandlung des frühen Mammakarzinoms sind über die Jahre immer wieder kleine, aber bedeutsame Fortschritte gemacht worden. In der Prävention gewinnen die sogenannten Panel-Gen-Analysen immer mehr an Bedeutung, da das durch die getesteten Gene bedingte Risiko immer besser verstanden wird und somit Konzepte für die Integration in die Krankenversorgung erarbeitet werden können. In der adjuvanten Situation konnte die erste Studie in der sogenannten postneoadjuvanten Situation bei fehlender pathologischer Komplettremission nach Trastuzumab oder Pertuzumab + Trastuzumab eine deutliche Verbesserung der Prognose zeigen. Weitere Studien mit diesem postneoadjuvanten Therapiekonzept werden zurzeit noch durchgeführt. Die CDK4/6-Inhibitoren, die in der metastasierten Situation eine deutliche Verbesserung des progressionsfreien Überlebens gezeigt hatten, werden zurzeit in der adjuvanten Situation in großen Therapiestudien getestet. Diese und weitere neue Daten zur Behandlung oder Prävention des primären Mammakarzinoms werden in dieser Übersichtsarbeit vor dem Hintergrund aktueller Studien vorgestellt., 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.

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., In der Prävention und Behandlung des frühen Mammakarzinoms sind über die Jahre immer wieder kleine, aber bedeutsame Fortschritte gemacht worden. In der Prävention gewinnen die sogenannten Panel-Gen-Analysen immer mehr an Bedeutung, da das durch die getesteten Gene bedingte Risiko immer besser verstanden wird und somit Konzepte für die Integration in die Krankenversorgung erarbeitet werden können. In der adjuvanten Situation konnte die erste Studie in der sogenannten postneoadjuvanten Situation bei fehlender pathologischer Komplettremission nach Trastuzumab oder Pertuzumab + Trastuzumab eine deutliche Verbesserung der Prognose zeigen. Weitere Studien mit diesem postneoadjuvanten Therapiekonzept werden zurzeit noch durchgeführt. Die CDK4/6-Inhibitoren, die in der metastasierten Situation eine deutliche Verbesserung des progressionsfreien Überlebens gezeigt hatten, werden zurzeit in der adjuvanten Situation in großen Therapiestudien getestet. Diese und weitere neue Daten zur Behandlung oder Prävention des primären Mammakarzinoms werden in dieser Übersichtsarbeit vor dem Hintergrund aktueller Studien vorgestellt.

Die Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom hat sich in den letzten Jahren weiterentwickelt. Zusätzlich zum Therapiefortschritt in den etablierten Subgruppen (Hormonrezeptor- und HER2-Status) gibt es nun Therapien, die sich an einzelnen molekularen Charakteristika orientieren, wie zum Beispiel die PARP-Inhibitortherapie bei BRCA-mutierten Patientinnen. Zusätzlich dazu sind Tests in der Entwicklung, die innerhalb von Subgruppen weitere Marker etablieren sollen, um die Wirksamkeit einer Therapie vorherzusagen. Die PI3K-Mutationstestung bei HER2-negativen, hormonrezeptorpositiven Tumoren, und die PD-L1-Testung von Immunzellen bei triple-negativen Tumoren werden voraussichtlich in der klinischen Praxis etabliert, um Patientinnen für die jeweiligen Therapien auszuwählen. Mit neuen Therapieansätzen treten auch neue Nebenwirkungen auf. Das Management dieser Nebenwirkungen ebenso wie die der klassischen Therapien (supportive Therapie) ist mit der Einführung neuer Behandlungen essenziell, um die Lebensqualität der Patientinnen zu erhalten. Das Wissen über Maßnahmen zur Erhaltung und Verbesserung der Lebensqualität hat in den letzten Jahren deutlich zugenommen. Lifestyle-Faktoren sollten dabei ebenso Berücksichtigung finden wie moderne Therapieverfahren. Diese Übersichtsarbeit fasst die neuesten Studien und Veröffentlichungen zusammen und bewertet sie in Bezug auf die Relevanz für die klinische Praxis., 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, hormone-receptor-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 patientsʼ 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.

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, hormone-receptor-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 patientsʼ 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., Die Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom hat sich in den letzten Jahren weiterentwickelt. Zusätzlich zum Therapiefortschritt in den etablierten Subgruppen (Hormonrezeptor- und HER2-Status) gibt es nun Therapien, die sich an einzelnen molekularen Charakteristika orientieren, wie zum Beispiel die PARP-Inhibitortherapie bei BRCA-mutierten Patientinnen. Zusätzlich dazu sind Tests in der Entwicklung, die innerhalb von Subgruppen weitere Marker etablieren sollen, um die Wirksamkeit einer Therapie vorherzusagen. Die PI3K-Mutationstestung bei HER2-negativen, hormonrezeptorpositiven Tumoren, und die PD-L1-Testung von Immunzellen bei triple-negativen Tumoren werden voraussichtlich in der klinischen Praxis etabliert, um Patientinnen für die jeweiligen Therapien auszuwählen. Mit neuen Therapieansätzen treten auch neue Nebenwirkungen auf. Das Management dieser Nebenwirkungen ebenso wie die der klassischen Therapien (supportive Therapie) ist mit der Einführung neuer Behandlungen essenziell, um die Lebensqualität der Patientinnen zu erhalten. Das Wissen über Maßnahmen zur Erhaltung und Verbesserung der Lebensqualität hat in den letzten Jahren deutlich zugenommen. Lifestyle-Faktoren sollten dabei ebenso Berücksichtigung finden wie moderne Therapieverfahren. Diese Übersichtsarbeit fasst die neuesten Studien und Veröffentlichungen zusammen und bewertet sie in Bezug auf die Relevanz für die klinische Praxis.

Self-efficacy is associated with both academic performance and attrition in higher education. Whether it is possible to measure students’ academic self-efficacy after admission and prior to commencing higher education (i.e. pre-academic self-efficacy) in a valid and reliable way has hardly been studied. Aims: 1) to evaluate the construct validity and psychometric properties of two short scales to measure Pre-Academic Learning Self-Efficacy (PAL-SE) and Pre-Academic Exam Self-Efficacy (PAE-SE) using Rasch measurement models, 2) to investigate whether pre-academic self-efficacy was associated with half-year attrition across degree programs and institutions. Data consisted of 2686 Danish students admitted to nine different university degree programs across two institutions. Item analyses showed both scales to be essentially objective and construct valid, however, all items from the PAE-SE and two from the PAL-SE were locally dependent. Differential item functioning was found for the PAL-SE relative to degree programs. Reliability of the PAE-SE was .77, and varied for the PAL-SE from .79 to .86 across degree programs. Targeting was good only for the PAL-SE, thus we proceeded with the PAL-SE. PAL-SE was found to be associated with half-year attrition: A difference in PAL-SE from minimum to maximum was associated with a difference in half-year attrition of approximately 7%. This association was found both in the bivariate model and in the multivariate models with control of degree program, and with control of degree program and individual covariates such as earlier educational achievement and social background variables. Results thus also indicate that PAL-SE has a causal effect on half-year attrition.