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1. Physical activity and Mediterranean diet as potential modulators of osteoprotegerin and soluble RANKL in gBRCA1/2 mutation carriers: results of the lifestyle intervention pilot study LIBRE-1

Author

Neirich, Leonie, Yahiaoui-Doktor, Maryam, Lammert, Jacqueline, Basrai, Maryam, Seethaler, Benjamin, Berling-Ernst, Anika, Ramser, Juliane, Quante, Anne S., Schmidt, Thorsten, Niederberger, Uwe, Rhiem, Kerstin, Schmutzler, Rita, Engel, Christoph, Bischoff, Stephan C., Halle, Martin, Kiechle, Marion, and Grill, Sabine

Published
2021
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4. Precursor fractions of neurotensin and enkephalin might point to molecular mechanisms of cancer risk modulation during a lifestyle-intervention in germline BRCA1/2 gene mutation carriers

Author

Grill, Sabine, Yahiaoui-Doktor, Maryam, Basrai, Maryam, Struck, Joachim, Schulte, Janin, Berling-Ernst, Anika, Engel, Christoph, Ullrich, Mirjam, Lammert, Jacqueline, Bischoff, Stephan C., Schmidt, Thorsten, Niederberger, Uwe, Chronas, Dimitrios, Rhiem, Kerstin, Schmutzler, Rita, Halle, Martin, and Kiechle, Marion

Published
2021
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6. Community-driven development of a modified progression-free survival ratio for precision oncology

Author

Mock, Andreas, Heilig, Christoph E, Kreutzfeldt, Simon, Huebschmann, Daniel, Heining, Christoph, Schröck, Evelin, Brors, Benedikt, Stenzinger, Albrecht, Jäger, Dirk, Schlenk, Richard, Glimm, Hanno, Fröhling, Stefan, Horak, Peter, Apostolidis, Leonidas, Augustin, Marinela, Aust, Daniela, Bhatti, Irfan Ahmed, Bloehdorn, Johannes, Brendel, Cornelia, Britschgi, Christian, Braess, Jan, Burdach, Stefan, Busch, Elena, Casuscelli, Jozefina, Desuki, Alexander, Deutsch, Thomas, Dietrich, Mareike, Ehmer, Ursula, Ettrich, Thomas J, Falkenhorst, Johanna, Fehm, Tanja, Flörcken, Anne, Forschner, Andrea, Fuxius, Stefan, Gonzales-Carmona, Maria, Griesinger, Frank, Grill, Sabine, Gröschel, Stefan, Haag, Georg Martin, Haag, Ulrich, Halama, Niels, Hebart, Holger, Heidger, Nina, Hermes, Barbara, Hess, Georg, Hettmer, Simone, Hoechstetter, Manuela, Hoffmann, Martin, Hüttner, Felix J, Illert, Anna L, Jenzer, Maximilian, Kasper, Bernd, Kasper-Virchow, Stefan, Kindler, Thomas, Koscielniak, Ewa, Krönke, Jan, Kühn, Michael, Kunzmann, Volker, Lang, Alois, Leichsenring, Jonas, Livingstone, Elisabeth, Liotta, Lucia, Luley, Kim, Mack, Elisabeth, Martens, Uwe M, Metzeler, Klaus, Middeke, Jan Moritz, Möhrmann, Lino, Jayarama-Naidu, Roopa, Pape, Ulrich-Frank, Perkhofer, Lukas, Pfeufer, Arne, Pixberg, Constantin, Quante, Michael, Rendenbach, Bernhard, Rieke, Damian, Rothermundt, Christian, Sagerer, Andre Norbert, Salzmann, Martin, Saur, Dieter, Schilling, Bastian, Schleicher, Jan, Schlenska-Lange, Anke, Schmidt, Thomas, Schmitz, Sophia, Schölch, Sebastian, Shah, Rajiv, Shoumariyeh, Khalid, Siebenhüner, Alexander, Singh, Martin, Siveke, Jens, Springfeld, Christoph, Starke, Helen, Strobel, Sophia, Teleanu, Veronica, Thon, Niklas, Wagner, Sebastian, Walle, Thomas, Westphalen, Benedikt, Whitlock, Bettina, Winkler, Eva, Wirsik, Naita Maren, Woydack, Lena, Bois, Angelika Zabel-du, and Zschäbitz, Stefanie

Published
2019
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9. Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer

Author

Rhiem, Kerstin, Zachariae, Silke, Waha, Anke, Grill, Sabine, Hester, Anna, Golatta, Michael; https://orcid.org/0000-0002-2605-0060, van Mackelenbergh, Marion, Fehm, Tanja, Schlaiß, Tanja, Ripperger, Tim; https://orcid.org/0000-0001-6470-8612, Ledig, Susanne, Meisel, Cornelia, Speiser, Dorothee; https://orcid.org/0000-0002-6447-629X, Veselinovic, Kristina, Schröder, Christopher, Witzel, Isabell; https://orcid.org/0000-0002-8734-4521, Gallwas, Julia, Weber, Bernhard H F; https://orcid.org/0000-0002-8808-7723, Solbach, Christine; https://orcid.org/0000-0001-8284-3199, Aktas, Bariyhe, Hahnen, Eric, Engel, Christoph; https://orcid.org/0000-0002-7247-282X, Schmutzler, Rita, Rhiem, Kerstin, Zachariae, Silke, Waha, Anke, Grill, Sabine, Hester, Anna, Golatta, Michael; https://orcid.org/0000-0002-2605-0060, van Mackelenbergh, Marion, Fehm, Tanja, Schlaiß, Tanja, Ripperger, Tim; https://orcid.org/0000-0001-6470-8612, Ledig, Susanne, Meisel, Cornelia, Speiser, Dorothee; https://orcid.org/0000-0002-6447-629X, Veselinovic, Kristina, Schröder, Christopher, Witzel, Isabell; https://orcid.org/0000-0002-8734-4521, Gallwas, Julia, Weber, Bernhard H F; https://orcid.org/0000-0002-8808-7723, Solbach, Christine; https://orcid.org/0000-0001-8284-3199, Aktas, Bariyhe, Hahnen, Eric, Engel, Christoph; https://orcid.org/0000-0002-7247-282X, and Schmutzler, Rita

Abstract

Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in BRCA1, BRCA2, and nine additional cancer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis. Patients and Methods: In 1,600 women with sTNBC (median age at diagnosis: 41 years, range 19–78 years), we investigated the association between age at diagnosis and PV occurrence in cancer predisposition genes using logistic regression. Results: 260 sTNBC patients (16.2%) were found to have a PV in cancer predisposition genes (BRCA1: n = 170 [10.6%]; BRCA2: n = 46 [2.9%], other: n = 44 [2.8%]). The PV prevalence in women diagnosed between 50 and 59 years (n = 194) was 11.3% (22/194). Logistic regression showed a significant increase in PV prevalence with decreasing age at diagnosis (OR 1.41 per 10 years younger age at diagnosis; 95% confidence interval: 1.21–1.65; p < 0.001). The PV prevalence predicted by the model was above 10% for diagnoses before the age of 56.8 years. Conclusion: Based on the data presented, we recommend genetic testing by gene panel analysis for sTNBC patients diagnosed before the age of 60 years. Due to the still uncertain estimate for women with sTNBC diagnosed above the age of 60 years, further studies are needed.

Published
2023

10. Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer

Author

Rhiem, Kerstin, primary, Zachariae, Silke, additional, Waha, Anke, additional, Grill, Sabine, additional, Hester, Anna, additional, Golatta, Michael, additional, van Mackelenbergh, Marion, additional, Fehm, Tanja, additional, Schlaiß, Tanja, additional, Ripperger, Tim, additional, Ledig, Susanne, additional, Meisel, Cornelia, additional, Speiser, Dorothee, additional, Veselinovic, Kristina, additional, Schröder, Christopher, additional, Witzel, Isabell, additional, Gallwas, Julia, additional, Weber, Bernhard H.F., additional, Solbach, Christine, additional, Aktas, Bariyhe, additional, Hahnen, Eric, additional, Engel, Christoph, additional, and Schmutzler, Rita, additional

Published
2023
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11. Smoking and physical inactivity increase cancer prevalence in BRCA-1 and BRCA-2 mutation carriers: results from a retrospective observational analysis

Author

Grill, Sabine, Yahiaoui-Doktor, Maryam, Dukatz, Ricarda, Lammert, Jacqueline, Ullrich, Mirjam, Engel, Christoph, Pfeifer, Katharina, Basrai, Maryam, Siniatchkin, Michael, Schmidt, Thorsten, Weisser, Burkhard, Rhiem, Kerstin, Ditsch, Nina, Schmutzler, Rita, Bischoff, Stephan C., Halle, Martin, and Kiechle, Marion

Published
2017
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12. NCALD as a potential predictive biomarker for the efficacy of platinum-based chemotherapy in ovarian cancer

Author

Konrad, Sarah M, primary, Schwamborn, Kristina, additional, Krüger, Achim, additional, Honert, Katja, additional, Schmitt, Manfred, additional, Hellmann, Daniela, additional, Schmalfeldt, Barbara, additional, Meindl, Alfons, additional, Kiechle, Marion, additional, Quante, Anne S, additional, Brambs, Christine, additional, Grill, Sabine, additional, and Ramser, Juliane, additional

Published
2022
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15. Abstract A008: TP53 field defects in uterine fluid are associated with ovarian cancer risk

Author

Risques, Rosana, primary, Smith, Thomas H., additional, Norgaard, Zachary K., additional, Katz, Roniz, additional, Lo, Fang Yin, additional, Schmidt, Elizabeth K., additional, Higgins, Jacob E., additional, Filipits, Martin, additional, Labidi-Galy, Intidhar, additional, Cibula, David, additional, Dostálek, Lukáš, additional, Jelenek, Gabriel, additional, Plch, Magdalena, additional, Bouda, Jiří, additional, Mustea, Alexander, additional, Condic, Mateja, additional, Grill, Sabine, additional, Gleeson, Noreen, additional, Oppelt, Peter, additional, Pristauz-Telsnigg, Gunda, additional, Vanderstichele, Adriaan, additional, Obrecht, Siel, additional, Rosenthal, Adam, additional, Speiser, Paul, additional, and Salk, Jesse, additional

Published
2022
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16. Abstract PR005: TP53 field defects in uterine fluid are associated with ovarian cancer risk

Author

Risques, Rosana, primary, Smith, Thomas H., additional, Norgaard, Zachary K., additional, Katz, Roniz, additional, Lo, Fang Yin, additional, Schmidt, Elizabeth K., additional, Higgins, Jacob E., additional, Filipits, Martin, additional, Labidi-Galy, Intidhar, additional, Cibula, David, additional, Dostálek, Lukáš, additional, Jelenek, Gabriel, additional, Plch, Magdalena, additional, Bouda, Jiří, additional, Mustea, Alexander, additional, Condic, Mateja, additional, Grill, Sabine, additional, Gleeson, Noreen, additional, Oppelt, Peter, additional, Pristauz-Telsnigg, Gunda, additional, Vanderstichele, Adriaan, additional, Obrecht, Siel, additional, Rosenthal, Adam, additional, Speiser, Paul, additional, and Salk, Jesse, additional

Published
2022
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18. Breast cancer characteristics and surgery among women with Li‐Fraumeni syndrome in Germany—A retrospective cohort study

Author

Rippinger, Nathalie, primary, Fischer, Christine, additional, Sinn, Hans‐Peter, additional, Dikow, Nicola, additional, Sutter, Christian, additional, Rhiem, Kerstin, additional, Grill, Sabine, additional, Cremer, Friedrich W., additional, Nguyen, Huu P., additional, Ditsch, Nina, additional, Kast, Karin, additional, Hettmer, Simone, additional, Kratz, Christian P., additional, and Schott, Sarah, additional

Published
2021
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19. Consensus Recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Rhiem, Kerstin, primary, Auber, Bernd, additional, Briest, Susanne, additional, Dikow, Nicola, additional, Ditsch, Nina, additional, Dragicevic, Neda, additional, Grill, Sabine, additional, Hahnen, Eric, additional, Horvath, Judit, additional, Jaeger, Bernadette, additional, Kast, Karin, additional, Kiechle, Marion, additional, Leinert, Elena, additional, Morlot, Susanne, additional, Püsken, Michael, additional, Schäfer, Dieter, additional, Schott, Sarah, additional, Schroeder, Christopher, additional, Siebers-Renelt, Ulrike, additional, Solbach, Christine, additional, Weber-Lassalle, Nana, additional, Witzel, Isabell, additional, Zeder-Göß, Christine, additional, and Schmutzler, Rita K., additional

Published
2021
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20. Breast cancer characteristics and surgery among women with Li-Fraumeni syndrome in Germany-A retrospective cohort study

Author

Rippinger, Nathalie, Fischer, Christine, Sinn, Hans-Peter, Dikow, Nicola, Sutter, Christian, Rhiem, Kerstin, Grill, Sabine, Cremer, Friedrich W., Nguyen, Huu P., Ditsch, Nina, Kast, Karin, Hettmer, Simone, Kratz, Christian P., Schott, Sarah, Rippinger, Nathalie, Fischer, Christine, Sinn, Hans-Peter, Dikow, Nicola, Sutter, Christian, Rhiem, Kerstin, Grill, Sabine, Cremer, Friedrich W., Nguyen, Huu P., Ditsch, Nina, Kast, Karin, Hettmer, Simone, Kratz, Christian P., and Schott, Sarah

Abstract

Background Women with Li-Fraumeni syndrome (LFS) have elevated breast cancer (BC) risk. Optimal BC treatment strategies in this population are yet unknown. Methods BC subtypes and treatment were retrospectively investigated between December 2016 and January 2019 in a multicentre study. BC risks were evaluated according to the type of surgery. Results Thirty-five women of our study population (35/44; 79.5%) had developed 36 breast lesions at first diagnosis at a mean age of 34 years. Those breast lesions comprised 32 invasive BCs (89%), three ductal carcinoma in situ alone (8%) and one malignant phyllodes tumour (3%). BCs were mainly high-grade (18/32), of no special type (NST; 31/32), HER2-enriched (11/32) or luminal-B-(like)-type (10/32). Affected women (n = 35) received breast-conserving surgery (BCS, n = 17) or a mastectomy (ME, n = 18) including seven women with simultaneous contralateral prophylactic mastectomy (CPM) at first diagnosis. Nineteen women suffered 20 breast or locoregional axillary lesions at second diagnosis with mean age of 36. Median time between first and second diagnosis was 57 months; median time to contra- and ipsilateral recurrence depended on surgical strategies (BCS: 46 vs. unilateral ME: 93 vs. bilateral ME > 140 months). Women with a primary treatment of solitaire therapeutic ME suffered from contralateral BC earlier compared to those with therapeutic ME and CPM (median: 93 vs. >140 months). Conclusion Aggressive BC subtypes occur among women with LFS. Surgical treatment, i.e. ME and CPM, may prolong time to a second BC diagnosis. Conclusion on long-term survival benefit is pending. Individual competing tumour risks and long-term outcomes need to be taken into consideration.

Published
2021

21. Consensus Recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Rhiem, Kerstin E. M., Auber, Bernd, Briest, Susanne, Dikow, Nicola, Ditsch, Nina, Dragicevic, Neda, Grill, Sabine, Hahnen, Eric Thomas, Horváth, Judit, Jäger, Bernadette, Kast, Karin, Kiechle, Marion, Leinert, Elena, Morlot, Susanne, Püsken, Michael, Schäfer, Dieter, Schott, Sarah, Schroeder, Christopher Maximilian, Siebers-Renelt, Ulrike, Solbach, Christine, Weber-Lassalle, Nana-Maureen, Witzel, Isabell, Zeder-Göß, Christine, Schmutzler, Rita, Rhiem, Kerstin E. M., Auber, Bernd, Briest, Susanne, Dikow, Nicola, Ditsch, Nina, Dragicevic, Neda, Grill, Sabine, Hahnen, Eric Thomas, Horváth, Judit, Jäger, Bernadette, Kast, Karin, Kiechle, Marion, Leinert, Elena, Morlot, Susanne, Püsken, Michael, Schäfer, Dieter, Schott, Sarah, Schroeder, Christopher Maximilian, Siebers-Renelt, Ulrike, Solbach, Christine, Weber-Lassalle, Nana-Maureen, Witzel, Isabell, Zeder-Göß, Christine, and Schmutzler, Rita

Abstract

Background: The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has established a multigene panel (TruRisk®) for the analysis of risk genes for familial breast and ovarian cancer. Summary: An interdisciplinary team of experts from the GC-HBOC has evaluated the available data on risk modification in the presence of pathogenic mutations in these genes based on a structured literature search and through a formal consensus process. Key Messages: The goal of this work is to better assess individual disease risk and, on this basis, to derive clinical recommendations for patient counseling and care at the centers of the GC-HBOC from the initial consultation prior to genetic testing to the use of individual risk-adapted preventive/therapeutic measures.

Published
2021

22. Mathematikbezogene affektive Schülermerkmale fördern: Eine explorative Untersuchung zum Potential von Fermi-Aufgaben

Author

Reinhold, Frank, Strohmaier, Anselm, and Grill, Sabine

Abstract

Mathematikbezogene affektive Merkmale wie Ängstlichkeit, Selbstwirksamkeit und Interesse können das Lernen von Mathematik beeinflussen. Wir stellen auf der Basis einzelner prototypischer Prozesse des Modellierungskreislaufes dar, warum gerade Fermi-Aufgaben ein großes Potential für die positive Beeinflussung dieser Schülermerkmale haben können und sie damit zur Förderung von Schülerinnen und Schülern im Kontext mehrdimensionaler Bildungsziele im Mathematikunterricht beitragen können. Zudem berichten wir von einer explorativen Untersuchung mit 30 Schülerinnen und Schülern zweier zehnter Klassen einer Berufsoberschule, deren Ergebnisse verträglich mit dieser Vermutung sind., mathematica didactica , Vol. 43 No. 2 (2020)

Published
2020
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23. Cancer surveillance and distress among adult pathogenicTP53germline variant carriers in Germany: A multicenter feasibility and acceptance survey

Author

Rippinger, Nathalie, Fischer, Christine, Haun, Markus W., Rhiem, Kerstin, Grill, Sabine, Kiechle, Marion, Cremer, Friedrich W., Kast, Karin, Nguyen, Huu P., Ditsch, Nina, Kratz, Christian P., Vogel, Julia, Speiser, Dorothee, Hettmer, Simone, Glimm, Hanno, Froehling, Stefan, Jaeger, Dirk, Seitz, Stephan, Hahne, Andrea, Maatouk, Imad, Sutter, Christian, Schmutzler, Rita K., Dikow, Nicola, Schott, Sarah, Rippinger, Nathalie, Fischer, Christine, Haun, Markus W., Rhiem, Kerstin, Grill, Sabine, Kiechle, Marion, Cremer, Friedrich W., Kast, Karin, Nguyen, Huu P., Ditsch, Nina, Kratz, Christian P., Vogel, Julia, Speiser, Dorothee, Hettmer, Simone, Glimm, Hanno, Froehling, Stefan, Jaeger, Dirk, Seitz, Stephan, Hahne, Andrea, Maatouk, Imad, Sutter, Christian, Schmutzler, Rita K., Dikow, Nicola, and Schott, Sarah

Abstract

Background Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome caused by pathogenic germline variants ofTP53. Cancer surveillance has noted a significant survival advantage in individuals with LFS; however, little is known about the feasibility, acceptance, and psychosocial effects of such a program. Methods PathogenicTP53germline variant carriers completed a 7-part questionnaire evaluating sociodemographics, cancer history, surveillance participation, reasons for nonadherence, worries, and distress adapted from the Cancer Worry Scale. Counselees' common concerns and suggestions were assessed in MAXQDA Analytics Pro 12. Results Forty-nine participants (46 females and 3 males), aged 40.0 +/- 12.6 years, formed the study population; 43 (88%) had a personal cancer history (including multiple cancers in 10 [20%]). Forty-three individuals participated (88%) in surveillance during the study or formerly. Willingness to undergo surveillance was influenced by satisfaction with genetic testing and counseling (P = .019 [Fisher-Yates test]) but not by sociodemographics, cancer history, or distress level. Almost one-third of the participants reported logistical difficulties in implementing surveillance because of the high frequency of medical visits, scheduling difficulties, and the travel distance to their surveillance providers. Self-reported distress and perceived emotional burden for family members and partners were moderate (median for self-reported distress, 3.3; median for perceived emotional burden, 3.0). For both, the interquartile range was moderate to very high (2.7-3.7 and 3.0-3.7, respectively). Conclusions Individuals with LFS require efficient counseling as well as an accessible, well-organized, interdisciplinary, standardized surveillance program to increase adherence and psychological coping.

Published
2020

25. Consensus Recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer.

Author

Rhiem, Kerstin, Auber, Bernd, Briest, Susanne, Dikow, Nicola, Ditsch, Nina, Dragicevic, Neda, Grill, Sabine, Hahnen, Eric, Horvath, Judit, Jaeger, Bernadette, Kast, Karin, Kiechle, Marion, Leinert, Elena, Morlot, Susanne, Püsken, Michael, Schäfer, Dieter, Schott, Sarah, Schroeder, Christopher, Siebers-Renelt, Ulrike, and Solbach, Christine

Subjects
CONSENSUS (Social sciences), CANCER genetics
Abstract

Background: The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has established a multigene panel (TruRisk®) for the analysis of risk genes for familial breast and ovarian cancer. Summary: An interdisciplinary team of experts from the GC-HBOC has evaluated the available data on risk modification in the presence of pathogenic mutations in these genes based on a structured literature search and through a formal consensus process. Key Messages: The goal of this work is to better assess individual disease risk and, on this basis, to derive clinical recommendations for patient counseling and care at the centers of the GC-HBOC from the initial consultation prior to genetic testing to the use of individual risk-adapted preventive/therapeutic measures. [ABSTRACT FROM AUTHOR]

Published
2022
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26. TP53 germline mutations in the context of families with hereditary breast and ovarian cancer: a clinical challenge

Author

Grill, Sabine, primary, Ramser, Juliane, additional, Hellebrand, Heide, additional, Pfarr, Nicole, additional, Boxberg, Melanie, additional, Brambs, Christine, additional, Ditsch, Nina, additional, Meindl, Alfons, additional, Groß, Eva, additional, Meitinger, Thomas, additional, Kiechle, Marion, additional, and Quante, Anne S., additional

Published
2020
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27. Cancer surveillance and distress among adult pathogenic TP53 germline variant carriers in Germany: A multicenter feasibility and acceptance survey

Author

Rippinger, Nathalie, primary, Fischer, Christine, additional, Haun, Markus W., additional, Rhiem, Kerstin, additional, Grill, Sabine, additional, Kiechle, Marion, additional, Cremer, Friedrich W., additional, Kast, Karin, additional, Nguyen, Huu P., additional, Ditsch, Nina, additional, Kratz, Christian P., additional, Vogel, Julia, additional, Speiser, Dorothee, additional, Hettmer, Simone, additional, Glimm, Hanno, additional, Fröhling, Stefan, additional, Jäger, Dirk, additional, Seitz, Stephan, additional, Hahne, Andrea, additional, Maatouk, Imad, additional, Sutter, Christian, additional, Schmutzler, Rita K., additional, Dikow, Nicola, additional, and Schott, Sarah, additional

Published
2020
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29. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., Spurdle, Amanda B., Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., and Spurdle, Amanda B.

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

30. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., primary, Tudini, Emma, additional, Li, Hongyan, additional, Hahnen, Eric, additional, Wappenschmidt, Barbara, additional, Feliubadaló, Lidia, additional, Aalfs, Cora M., additional, Agata, Simona, additional, Aittomäki, Kristiina, additional, Alducci, Elisa, additional, Alonso‐Cerezo, María Concepción, additional, Arnold, Norbert, additional, Auber, Bernd, additional, Austin, Rachel, additional, Azzollini, Jacopo, additional, Balmaña, Judith, additional, Barbieri, Elena, additional, Bartram, Claus R., additional, Blanco, Ana, additional, Blümcke, Britta, additional, Bonache, Sandra, additional, Bonanni, Bernardo, additional, Borg, Åke, additional, Bortesi, Beatrice, additional, Brunet, Joan, additional, Bruzzone, Carla, additional, Bucksch, Karolin, additional, Cagnoli, Giulia, additional, Caldés, Trinidad, additional, Caliebe, Almuth, additional, Caligo, Maria A., additional, Calvello, Mariarosaria, additional, Capone, Gabriele L., additional, Caputo, Sandrine M., additional, Carnevali, Ileana, additional, Carrasco, Estela, additional, Caux‐Moncoutier, Virginie, additional, Cavalli, Pietro, additional, Cini, Giulia, additional, Clarke, Edward M., additional, Concolino, Paola, additional, Cops, Elisa J., additional, Cortesi, Laura, additional, Couch, Fergus J., additional, Darder, Esther, additional, Hoya, Miguel, additional, Dean, Michael, additional, Debatin, Irmgard, additional, Del Valle, Jesús, additional, Delnatte, Capucine, additional, Derive, Nicolas, additional, Diez, Orland, additional, Ditsch, Nina, additional, Domchek, Susan M., additional, Dutrannoy, Véronique, additional, Eccles, Diana M., additional, Ehrencrona, Hans, additional, Enders, Ute, additional, Evans, D. Gareth, additional, Farra, Chantal, additional, Faust, Ulrike, additional, Felbor, Ute, additional, Feroce, Irene, additional, Fine, Miriam, additional, Foulkes, William D., additional, Galvao, Henrique C.R., additional, Gambino, Gaetana, additional, Gehrig, Andrea, additional, Gensini, Francesca, additional, Gerdes, Anne‐Marie, additional, Germani, Aldo, additional, Giesecke, Jutta, additional, Gismondi, Viviana, additional, Gómez, Carolina, additional, Garcia, Encarna B., additional, González, Sara, additional, Grau, Elia, additional, Grill, Sabine, additional, Gross, Eva, additional, Guerrieri‐Gonzaga, Aliana, additional, Guillaud‐Bataille, Marine, additional, Gutiérrez‐Enríquez, Sara, additional, Haaf, Thomas, additional, Hackmann, Karl, additional, Hansen, Thomas V.O., additional, Harris, Marion, additional, Hauke, Jan, additional, Heinrich, Tilman, additional, Hellebrand, Heide, additional, Herold, Karen N., additional, Honisch, Ellen, additional, Horvath, Judit, additional, Houdayer, Claude, additional, Hübbel, Verena, additional, Iglesias, Silvia, additional, Izquierdo, Angel, additional, James, Paul A., additional, Janssen, Linda A.M., additional, Jeschke, Udo, additional, Kaulfuß, Silke, additional, Keupp, Katharina, additional, Kiechle, Marion, additional, Kölbl, Alexandra, additional, Krieger, Sophie, additional, Kruse, Torben A., additional, Kvist, Anders, additional, Lalloo, Fiona, additional, Larsen, Mirjam, additional, Lattimore, Vanessa L., additional, Lautrup, Charlotte, additional, Ledig, Susanne, additional, Leinert, Elena, additional, Lewis, Alexandra L., additional, Lim, Joanna, additional, Loeffler, Markus, additional, López‐Fernández, Adrià, additional, Lucci‐Cordisco, Emanuela, additional, Maass, Nicolai, additional, Manoukian, Siranoush, additional, Marabelli, Monica, additional, Matricardi, Laura, additional, Meindl, Alfons, additional, Michelli, Rodrigo D., additional, Moghadasi, Setareh, additional, Moles‐Fernández, Alejandro, additional, Montagna, Marco, additional, Montalban, Gemma, additional, Monteiro, Alvaro N., additional, Montes, Eva, additional, Mori, Luigi, additional, Moserle, Lidia, additional, Müller, Clemens R., additional, Mundhenke, Christoph, additional, Naldi, Nadia, additional, Nathanson, Katherine L., additional, Navarro, Matilde, additional, Nevanlinna, Heli, additional, Nichols, Cassandra B., additional, Niederacher, Dieter, additional, Nielsen, Henriette R., additional, Ong, Kai‐ren, additional, Pachter, Nicholas, additional, Palmero, Edenir I., additional, Papi, Laura, additional, Pedersen, Inge Sokilde, additional, Peissel, Bernard, additional, Perez‐Segura, Pedro, additional, Pfeifer, Katharina, additional, Pineda, Marta, additional, Pohl‐Rescigno, Esther, additional, Poplawski, Nicola K., additional, Porfirio, Berardino, additional, Quante, Anne S., additional, Ramser, Juliane, additional, Reis, Rui M., additional, Revillion, Françoise, additional, Rhiem, Kerstin, additional, Riboli, Barbara, additional, Ritter, Julia, additional, Rivera, Daniela, additional, Rofes, Paula, additional, Rump, Andreas, additional, Salinas, Monica, additional, Sánchez de Abajo, Ana María, additional, Schmidt, Gunnar, additional, Schoenwiese, Ulrike, additional, Seggewiß, Jochen, additional, Solanes, Ares, additional, Steinemann, Doris, additional, Stiller, Mathias, additional, Stoppa‐Lyonnet, Dominique, additional, Sullivan, Kelly J., additional, Susman, Rachel, additional, Sutter, Christian, additional, Tavtigian, Sean V., additional, Teo, Soo H., additional, Teulé, Alex, additional, Thomassen, Mads, additional, Tibiletti, Maria Grazia, additional, Tischkowitz, Marc, additional, Tognazzo, Silvia, additional, Toland, Amanda E., additional, Tornero, Eva, additional, Törngren, Therese, additional, Torres‐Esquius, Sara, additional, Toss, Angela, additional, Trainer, Alison H., additional, Tucker, Katherine M., additional, Asperen, Christi J., additional, Mackelenbergh, Marion T., additional, Varesco, Liliana, additional, Vargas‐Parra, Gardenia, additional, Varon, Raymonda, additional, Vega, Ana, additional, Velasco, Ángela, additional, Vesper, Anne‐Sophie, additional, Viel, Alessandra, additional, Vreeswijk, Maaike P. G., additional, Wagner, Sebastian A., additional, Waha, Anke, additional, Walker, Logan C., additional, Walters, Rhiannon J., additional, Wang‐Gohrke, Shan, additional, Weber, Bernhard H. F., additional, Weichert, Wilko, additional, Wieland, Kerstin, additional, Wiesmüller, Lisa, additional, Witzel, Isabell, additional, Wöckel, Achim, additional, Woodward, Emma R., additional, Zachariae, Silke, additional, Zampiga, Valentina, additional, Zeder‐Göß, Christine, additional, Investigators, KConFab, additional, Lázaro, Conxi, additional, Nicolo, Arcangela, additional, Radice, Paolo, additional, Engel, Christoph, additional, Schmutzler, Rita K., additional, Goldgar, David E., additional, and Spurdle, Amanda B., additional

Published
2019
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32. Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Hauke, Jan, Horvath, Judit, Gross, Eva, Gehrig, Andrea, Honisch, Ellen, Hackmann, Karl, Schmidt, Gunnar, Arnold, Norbert, Faust, Ulrike, Sutter, Christian, Hentschel, Julia, Wang-Gohrke, Shan, Smogavec, Mateja, Weber, Bernhard H. F., Weber-Lassalle, Nana, Weber-Lassalle, Konstantin, Borde, Julika, Ernst, Corinna, Altmueller, Janine, Volk, Alexander E., Thiele, Holger, Huebbel, Verena, Nuernberg, Peter, Keupp, Katharina, Versmold, Beatrix, Pohl, Esther, Kubisch, Christian, Grill, Sabine, Paul, Victoria, Herold, Natalie, Lichey, Nadine, Rhiem, Kerstin, Ditsch, Nina, Ruckert, Christian, Wappenschmidt, Barbara, Auber, Bernd, Rump, Andreas, Niederacher, Dieter, Haaf, Thomas, Ramser, Juliane, Dworniczak, Bernd, Engel, Christoph, Meindl, Alfons, Schmutzler, Rita K., Hahnen, Eric, Hauke, Jan, Horvath, Judit, Gross, Eva, Gehrig, Andrea, Honisch, Ellen, Hackmann, Karl, Schmidt, Gunnar, Arnold, Norbert, Faust, Ulrike, Sutter, Christian, Hentschel, Julia, Wang-Gohrke, Shan, Smogavec, Mateja, Weber, Bernhard H. F., Weber-Lassalle, Nana, Weber-Lassalle, Konstantin, Borde, Julika, Ernst, Corinna, Altmueller, Janine, Volk, Alexander E., Thiele, Holger, Huebbel, Verena, Nuernberg, Peter, Keupp, Katharina, Versmold, Beatrix, Pohl, Esther, Kubisch, Christian, Grill, Sabine, Paul, Victoria, Herold, Natalie, Lichey, Nadine, Rhiem, Kerstin, Ditsch, Nina, Ruckert, Christian, Wappenschmidt, Barbara, Auber, Bernd, Rump, Andreas, Niederacher, Dieter, Haaf, Thomas, Ramser, Juliane, Dworniczak, Bernd, Engel, Christoph, Meindl, Alfons, Schmutzler, Rita K., and Hahnen, Eric

Abstract

The prevalence of germ line mutations in non-BRCA1/2 genes associated with hereditary breast cancer (BC) is low, and the role of some of these genes in BC predisposition and pathogenesis is conflicting. In this study, 5589 consecutive BC index patients negative for pathogenic BRCA1/2 mutations and 2189 female controls were screened for germ line mutations in eight cancer predisposition genes (ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D, and TP53). All patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germ line testing. The highest mutation prevalence was observed in the CHEK2 gene (2.5%), followed by ATM (1.5%) and PALB2 (1.2%). The mutation prevalence in each of the remaining genes was 0.3% or lower. Using Exome Aggregation Consortium control data, we confirm significant associations of heterozygous germ line mutations with BC for ATM (OR: 3.63, 95% CI: 2.67-4.94), CDH1 (OR: 17.04, 95% CI: 3.54-82), CHEK2 (OR: 2.93, 95% CI: 2.29-3.75), PALB2 (OR: 9.53, 95% CI: 6.25-14.51), and TP53 (OR: 7.30, 95% CI: 1.22-43.68). NBN germ line mutations were not significantly associated with BC risk (OR: 1.39, 95% CI: 0.73-2.64). Due to their low mutation prevalence, the RAD51C and RAD51D genes require further investigation. Compared with control datasets, predicted damaging rare missense variants were significantly more prevalent in CHEK2 and TP53 in BC index patients. Compared with the overall sample, only TP53 mutation carriers show a significantly younger age at first BC diagnosis. We demonstrate a significant association of deleterious variants in the CHEK2, PALB2, and TP53 genes with bilateral BC. Both, ATM and CHEK2, were negatively associated with triple-negative breast cancer (TNBC) and estrogen receptor (ER)-negative tumor phenotypes. A particularly high CHEK2 mutation prevalence (5.2%) was observed in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors.

Published
2018

33. Clinical relevance of kallikrein-related peptidase 9, 10, 11, and 15 mRNA expression in advanced high-grade serous ovarian cancer

Author

Geng, Xiaocong, Liu, Yueyang, Diersch, Sandra, Kotzsch, Matthias, Grill, Sabine, Weichert, Wilko, Kiechle, Marion, Magdolen, Viktor, and Dorn, Julia

Subjects
lcsh:Medicine, Gene Expression, Surgical and Invasive Medical Procedures, Gastroenterology and Hepatology, Real-Time Polymerase Chain Reaction, Biochemistry, Diagnostic Medicine, Breast Tumors, Breast Cancer, Medicine and Health Sciences, Genetics, Humans, RNA, Messenger, lcsh:Science, Ovarian Neoplasms, lcsh:R, Cancers and Neoplasms, Biology and Life Sciences, Ascites, Proteins, Proteases, Prognosis, Ovarian Cancer, Enzymes, Survival Rate, Oncology, Enzymology, Disease Progression, lcsh:Q, Female, Kallikreins, Gynecological Tumors, Biomarkers, Research Article
Abstract

KLK9, 10, 11, and 15 may represent potential cancer biomarkers for evaluating ovarian cancer prognosis. In the present study, we selected a homogeneous cohort including 139 patients of advanced high-grade serous ovarian cancer (FIGO stage III/IV) and assessed the mRNA levels of KLK9, 10, 11, and 15 in tumor tissue by quantitative PCR. No significant associations of KLK9, 10, 11, and 15 mRNA with established clinical parameters (residual tumor mass, ascitic fluid volume) were found. Pronounced correlations between KLK10/KLK11 (rs = 0.647) and between KLK9/KLK15 (rs = 0.716) mRNA, but not between other combinations, indicate coordinate expression of distinct pairs of peptidases. In univariate Cox regression analysis, elevated KLK11 mRNA levels were significantly linked with prolonged overall survival (OS; p = 0.021) and progression-free survival (PFS; p = 0.008). KLK15 mRNA levels showed a trend towards significance in case of OS (p = 0.06); KLK9 and KLK10 mRNA expression levels were not associated with patients' outcome. In multivariable Cox analysis, KLK11 mRNA expression levels, apart from residual tumor mass, remained an independent predictive marker for OS (p = 0.007) and PFS (p = 0.015). Here, elevated KLK15 mRNA expression levels turned out to be significantly related to prolonged OS (p = 0.025) as well. High KLK11 but not the other KLK mRNA levels can be considered as strong independent favorable prognostic factor in this major ovarian cancer subtype.

Published
2017

34. Biomarker für ein längeres Überleben .

Author

Boxberg, Melanie, Grill, Sabine, and Poremba, Christopher

Subjects
*GENOMICS, *MOLECULAR genetics, *METASTATIC breast cancer, *BREAST cancer, *THERAPEUTICS
Abstract

Ein umfassendes genomisches Tumorscreening kann bei Patient:innen mit einem fortgeschrittenen bzw. metastasierten Mammakarzinom gegebenenfalls neue Therapieoptionen eröffnen und Informationen über Resistenzmechanismen des Tumors hinsichtlich bestimmter Therapien liefern. Eine personalisierte Therapie könnte auch bei Brustkrebs die Gesamtansprechrate verbessern sowie das progressionsfreie Überleben und das Gesamtüberleben verlängern. [ABSTRACT FROM AUTHOR]

Published
2022
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35. Gene panel testing of 5589 BRCA1/2 -negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Hauke, Jan, primary, Horvath, Judit, additional, Groß, Eva, additional, Gehrig, Andrea, additional, Honisch, Ellen, additional, Hackmann, Karl, additional, Schmidt, Gunnar, additional, Arnold, Norbert, additional, Faust, Ulrike, additional, Sutter, Christian, additional, Hentschel, Julia, additional, Wang-Gohrke, Shan, additional, Smogavec, Mateja, additional, Weber, Bernhard H. F., additional, Weber-Lassalle, Nana, additional, Weber-Lassalle, Konstantin, additional, Borde, Julika, additional, Ernst, Corinna, additional, Altmüller, Janine, additional, Volk, Alexander E., additional, Thiele, Holger, additional, Hübbel, Verena, additional, Nürnberg, Peter, additional, Keupp, Katharina, additional, Versmold, Beatrix, additional, Pohl, Esther, additional, Kubisch, Christian, additional, Grill, Sabine, additional, Paul, Victoria, additional, Herold, Natalie, additional, Lichey, Nadine, additional, Rhiem, Kerstin, additional, Ditsch, Nina, additional, Ruckert, Christian, additional, Wappenschmidt, Barbara, additional, Auber, Bernd, additional, Rump, Andreas, additional, Niederacher, Dieter, additional, Haaf, Thomas, additional, Ramser, Juliane, additional, Dworniczak, Bernd, additional, Engel, Christoph, additional, Meindl, Alfons, additional, Schmutzler, Rita K., additional, and Hahnen, Eric, additional

Published
2018
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38. Feasibility of structured endurance training and Mediterranean diet in BRCA1 and BRCA2 mutation carriers - an interventional randomized controlled multicenter trial (LIBRE-1)

Author

Kiechle, Marion, Dukatz, Ricarda, Yahiaoui-Doktor, Maryam, Berling, Anika, Basrai, Maryam, Staiger, Vera, Niederberger, Uwe, Marter, Nicole, Lammert, Jacqueline, Grill, Sabine, Pfeifer, Katharina, Rhiem, Kerstin, Schmutzler, Rita K., Laudes, Matthias, Siniatchkin, Michael, Halle, Martin, Bischoff, Stephan C., Engel, Christoph, Kiechle, Marion, Dukatz, Ricarda, Yahiaoui-Doktor, Maryam, Berling, Anika, Basrai, Maryam, Staiger, Vera, Niederberger, Uwe, Marter, Nicole, Lammert, Jacqueline, Grill, Sabine, Pfeifer, Katharina, Rhiem, Kerstin, Schmutzler, Rita K., Laudes, Matthias, Siniatchkin, Michael, Halle, Martin, Bischoff, Stephan C., and Engel, Christoph

Abstract

Background: Women with pathogenic BRCA germline mutations have an increased risk for breast and ovarian cancer that seems to be modified by life-style factors. Though, randomized trials investigating the impact of lifestyle interventions on cancer prevention and prognosis in BRCA carriers are still missing. Methods: We implemented a multicenter, prospective randomized controlled trial in BRCA1/2 patients, comparing a lifestyle intervention group (IG) with a control group (CG) with the primary aim to prove feasibility. Intervention comprised a structured, individualized endurance training alongside nutrition education based on the Mediterranean diet (MD) for 3 months, plus monthly group training and regular telephone contact during the subsequent 9 months. The CG attended one session on healthy nutrition and the benefits of physical activity. Primary endpoints were feasibility, acceptance and satisfaction over 12 months. Furthermore, effects on physical fitness, diet profile, body mass index (BMI), quality of life and perceived stress were investigated. Results: Sixty-eight participants (mean age 41, mean BMI 23.2 kg/m(2)) were enrolled, of whom 55 (81%, 26 IG, 29 CG) completed 12 months. 73% (n = 26) participated in at least 70% of all intervention sessions. Predictors for drop-outs (19%; n = 13) or non-adherence (27%; n = 7) were not found. 73% rated the program highly and 80% would participate again. Severe adverse events did not occur. Positive effects in the IG compared to the CG were observed for secondary endpoints: BMI, MD eating pattern and stress levels. Conclusions: This lifestyle intervention was feasible, safe and well accepted. Positive results on eating habits, physical fitness and stress levels warrant a larger randomized trial.

Published
2017

39. Feasibility of structured endurance training and Mediterranean diet in BRCA1 and BRCA2 mutation carriers – an interventional randomized controlled multicenter trial (LIBRE-1)

Author

Kiechle, Marion, Dukatz, Ricarda, Yahiaoui-Doktor, Maryam, Berling, Anika, Basrai, Maryam, Staiger, Vera, Niederberger, Uwe, Marter, Nicole, Lammert, Jacqueline, Grill, Sabine, Pfeifer, Katharina, Rhiem, Kerstin, Schmutzler, Rita K., Laudes, Matthias, Siniatchkin, Michael, Halle, Martin, Bischoff, Stephan C., and Engel, Christoph

Subjects
ddc
Published
2016

41. Lifestyle intervention in BRCA1/2 mutation carriers: study protocol for a prospective, randomized, controlled clinical feasibility trial (LIBRE-1 study)

Author

Kiechle, Marion, Engel, Christoph, Berling, Anika, Hebestreit, Katrin, Bischoff, Stephan, Dukatz, Ricarda, Gerber, Wolf-Dieter, Siniatchkin, Michael, Pfeifer, Katharina, Grill, Sabine, Yahiaoui-Doktor, Maryam, Kirsch, Ellen, Niederberger, Uwe, Marter, Nicole, Enders, Ute, Löffler, Markus, Meindl, Alfons, Rhiem, Kerstin, Schmutzler, Rita, Erickson, Nicole, and Halle, Martin

Subjects
Lifestyle intervention, Study Protocol, Hereditary ovarian cancer, BRCA1, BRCA2, Hereditary breast cancer
Abstract

Background Women with highly penetrant BRCA mutations have a 55–60% lifetime risk for breast cancer and a 16–59% lifetime risk for ovarian cancer. However, penetrance differs interindividually, indicating that environmental and behavioral factors may modify this risk. These include lifestyle factors such as physical activity status, dietary habits, and body weight. The modification of penetrance by changing lifestyle factors has not thus far been investigated in a randomized trial in BRCA mutation carriers. Methods Therefore, we intend to enroll 60 BRCA1/2 mutation carriers in a pilot feasibility study (Lifestyle Intervention Study in Women with Hereditary Breast and Ovarian Cancer (LIBRE) pilot). This multi-center, prospective, controlled trial aims to randomize (1:1) participants into a (1) multi-factorial lifestyle intervention group (IG) versus (2) the control group with usual care (CG). The primary endpoint is feasibility and acceptance of a structured interdisciplinary lifestyle intervention program over 12 months (at least 70% of the patients to complete the 1-year intervention). Furthermore, the effects on physical fitness, BMI, quality of life, and stress coping capacity will be investigated. During the first 3 months, women in the IG will receive structured, individualized and mainly supervised endurance training of ≥18 MET*h/week (MET = metabolic equivalent task) and personal nutritional counseling based on the Mediterranean diet. During the subsequent 9 months, the IG will receive monthly group training sessions and regular telephone contacts for motivation, whereas the CG will only receive usual care (one general counseling on healthy nutrition and benefits of regular physical activity on health status). At randomization and subsequent time points (3, 6, 12 months), cardiopulmonary fitness will be assessed by spiroergometry and nutritional and psychological status by validated questionnaires. Discussion This pilot study will investigate the optimal strategy to improve physical fitness, nutritional habits, and psychological factors in women at high risk for developing breast or ovarian cancer. The results of this pilot feasibility study will be the basis for a larger prospective randomized trial including clinical events (LIBRE). Trial registration ClinicalTrials.gov, NCT02087592

Published
2016

42. Additional file 2: of Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial

Author

Kiechle, Marion, Engel, Christoph, Berling, Anika, Hebestreit, Katrin, Bischoff, Stephan, Dukatz, Ricarda, Siniatchkin, Michael, Pfeifer, Katharina, Grill, Sabine, Yahiaoui-Doktor, Maryam, Kirsch, Ellen, Niederberger, Uwe, Enders, Ute, LĂśffler, Markus, Meindl, Alfons, Rhiem, Kerstin, Schmutzler, Rita, Erickson, Nicole, and Halle, Martin

Abstract

SPIRIT flow diagram of the LIBRE study. (PDF 91Â kb)

Published
2016
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43. Additional file 1: of Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial

Author

Kiechle, Marion, Engel, Christoph, Berling, Anika, Hebestreit, Katrin, Bischoff, Stephan, Dukatz, Ricarda, Siniatchkin, Michael, Pfeifer, Katharina, Grill, Sabine, Yahiaoui-Doktor, Maryam, Kirsch, Ellen, Niederberger, Uwe, Enders, Ute, LĂśffler, Markus, Meindl, Alfons, Rhiem, Kerstin, Schmutzler, Rita, Erickson, Nicole, and Halle, Martin

Abstract

SPIRIT checklist. (PDF 262Â kb)

Published
2016
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44. Feasibility of structured endurance training and Mediterranean diet in BRCA1 and BRCA2 mutation carriers – an interventional randomized controlled multicenter trial (LIBRE-1)

Author

Kiechle, Marion, primary, Dukatz, Ricarda, additional, Yahiaoui-Doktor, Maryam, additional, Berling, Anika, additional, Basrai, Maryam, additional, Staiger, Vera, additional, Niederberger, Uwe, additional, Marter, Nicole, additional, Lammert, Jacqueline, additional, Grill, Sabine, additional, Pfeifer, Katharina, additional, Rhiem, Kerstin, additional, Schmutzler, Rita K., additional, Laudes, Matthias, additional, Siniatchkin, Michael, additional, Halle, Martin, additional, Bischoff, Stephan C., additional, and Engel, Christoph, additional

Published
2017
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45. Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial

Author

Kiechle, Marion, Engel, Christoph, Berling, Anika, Hebestreit, Katrin, Bischoff, Stephan C., Dukatz, Ricarda, Siniatchkin, Michael, Pfeifer, Katharina, Grill, Sabine, Yahiaoui-Doktor, Maryam, Kirsch, Ellen, Niederberger, Uwe, Enders, Ute, Löffler, Markus, Meindl, Alfons, Rhiem, Kerstin, Schmutzler, Rita, Erickson, Nicole, and Halle, Martin

Subjects
ddc
Published
2015

46. Lifestyle intervention in BRCA1/2 mutation carriers: study protocol for a prospective, randomized, controlled clinical feasibility trial (LIBRE-1 study)

Author

Kiechle, Marion, Engel, Christoph, Berling, Anika, Hebestreit, Katrin, Bischoff, Stephan, Dukatz, Ricarda, Gerber, Wolf-Dieter, Siniatchkin, Michael, Pfeifer, Katharina, Grill, Sabine, Yahiaoui-Doktor, Maryam, Kirsch, Ellen, Niederberger, Uwe, Marter, Nicole, Enders, Ute, Löffler, Markus, Meindl, Alfons, Rhiem, Kerstin, Schmutzler, Rita, Erickson, Nicole, and Halle, Martin

Subjects
ddc
Published
2015

47. Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial

Author

Kiechle, Marion, Engel, Christoph, Berling, Anika, Hebestreit, Katrin, Bischoff, Stephan C., Dukatz, Ricarda, Siniatchkin, Michael, Pfeifer, Katharina, Grill, Sabine, Yahiaoui-Doktor, Maryam, Kirsch, Ellen, Niederberger, Uwe, Enders, Ute, Loeffler, Markus, Meindl, Alfons, Rhiem, Kerstin, Schmutzler, Rita, Erickson, Nicole, Halle, Martin, Kiechle, Marion, Engel, Christoph, Berling, Anika, Hebestreit, Katrin, Bischoff, Stephan C., Dukatz, Ricarda, Siniatchkin, Michael, Pfeifer, Katharina, Grill, Sabine, Yahiaoui-Doktor, Maryam, Kirsch, Ellen, Niederberger, Uwe, Enders, Ute, Loeffler, Markus, Meindl, Alfons, Rhiem, Kerstin, Schmutzler, Rita, Erickson, Nicole, and Halle, Martin

Abstract

Background: Women with highly penetrant BRCA mutations have a 55-60 % lifetime risk for breast cancer and a 16-59 % lifetime risk of developing ovarian cancer. However, penetrance differs interindividually, indicating that environmental and behavioral factors may modify this risk. It is well documented that the risk for sporadic breast cancer disease can be modified by changing lifestyle factors that primarily include physical activity, dietary habits, and body weight. It can thus be hypothesized that the modification of these lifestyle factors may also influence the incidence and progression of cancer in BRCA mutation carriers. Methods/design: This multicenter, interdisciplinary, prospective, two-armed, randomized (1: 1) controlled trial aims to enroll a minimum of 600 BRCA1 and BRCA2 mutation carriers to partake in either a lifestyle intervention or usual care. The study primarily aims to demonstrate an improvement of nutritional behavior (adherence to the Mediterranean diet), body mass index, and physical fitness. Furthermore, the effects on quality of life, stress coping capacity, breast cancer incidence, and mortality will be investigated. The intervention group (IG) will receive a structured lifestyle intervention over 12 months, whereas the control group (CG) will only receive information regarding a healthy lifestyle. During the first 3 months, women in the IG will receive structured, individualized, and mainly supervised endurance training with a minimum of 18 MET-h physical activity per week and nutrition education based on the Mediterranean diet. Over the following 9 months, IG monthly group training sessions and regular telephone contacts will motivate study participants. The CG will receive one general training session about healthy nutrition in accordance with the recommendations of the German Society of Nutrition (standard of care in Germany) and the benefits of regular physical activity on health status. At randomization and subsequent time points (3

Published
2016

48. Influence of the sFlt-1/PlGF ratio on clinical decision-making in women with suspected preeclampsia

Author

Zenclussen, Ana Claudia, Klein, Evelyn, Schlembach, Dietmar, Ramoni, Angela, Langer, Elena, Bahlmann, Franz, Grill, Sabine, Schaffenrath, Helene, Does, Reinhard van der, Messinger, Diethelm, Verhagen-Kamerbeek, Wilma D. J., Reim, Manfred, Hund, Martin, Stepan, Holger, Zenclussen, Ana Claudia, Klein, Evelyn, Schlembach, Dietmar, Ramoni, Angela, Langer, Elena, Bahlmann, Franz, Grill, Sabine, Schaffenrath, Helene, Does, Reinhard van der, Messinger, Diethelm, Verhagen-Kamerbeek, Wilma D. J., Reim, Manfred, Hund, Martin, and Stepan, Holger

Abstract

Objective: To evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians’ decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice. Methods: A multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome. Results: In 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women (11.0%), the initial decision to hospitalize was changed to no hospitalization. In seven women (5.9%) the revised decision was hospitalization. All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p < 0.0001). Conclusions: The use of the soluble fms-like tyrosine kinase 1/placental growth factor test influenced clinical decision making towards appropriate hospitalization in a considerable proportion of women with suspected preeclampsia. This is the first study to demonstrate the impact of angiogenic biomarkers on decision making in a routine clinical practice.

Published
2016

49. A Randomized Trial of Polymer-Free Dual Drug-Eluting Stents versus Polymer-Based Cypher and Endeavor Drug-Eluting Stents in Patients with Coronary Artery Disease

Author

Grill, Sabine, Kastrati, Adnan (Prof. Dr.), and Laugwitz, Karl-Ludwig (Prof. Dr.)

Subjects
Medizin und Gesundheit, ddc:610
Abstract

In der klinischen Studie ISAR Test 2 gelingt erstmals eine erfolgreiche Inkorporierung von zwei aktiv medikamentösen Komponenten in das Gerüst eines medikamentenbeschichteten, polymerfreien Stents. Die größte Innovation dieses randomisierten klinischen Tests mit einem Kollektiv von 1007 Patienten, lag im Debut des Rapamycin und Probucol beschichteten polymerfreien Stents, welcher offensichtlich eine so gute antirestenotische Wirkung zeigte, dass er dem bisher als Goldstandard geltenden Sirolimus beschichteten Stent ebenbürtig erscheint. ISAR Test 2 was a randomized trial which compared the safety and efficacy of the sirolimus eluting stent Cypher, the zotarolimus eluting stent Endeavour as well as the new polymer-free dual drug eluting stent. As a conclusion this study reports the successful incorporation of rapamycin and probucol into a drug eluting stent platform without using a polymer based system. The main achievement of this described novel polymer free dual drug eluting stent was a significant antirestenotic efficacy, compared to that of the sirolimus eluting stent and even superior to that of the zotarolimus stent.

Published
2014

50. Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial

Author

Kiechle, Marion, primary, Engel, Christoph, additional, Berling, Anika, additional, Hebestreit, Katrin, additional, Bischoff, Stephan C., additional, Dukatz, Ricarda, additional, Siniatchkin, Michael, additional, Pfeifer, Katharina, additional, Grill, Sabine, additional, Yahiaoui-Doktor, Maryam, additional, Kirsch, Ellen, additional, Niederberger, Uwe, additional, Enders, Ute, additional, Löffler, Markus, additional, Meindl, Alfons, additional, Rhiem, Kerstin, additional, Schmutzler, Rita, additional, Erickson, Nicole, additional, and Halle, Martin, additional

Published
2016
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