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99 Publications visible to you, out of a total of 99
The budgetary impact of genetic testing for hereditary breast cancer for the statutory health insurance
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Objectives: Potential opportunities and challenges of predictive genetic risk classification of healthy persons are currently discussed. However, the budgetary impact of rising demand is uncertain. … This project aims to evaluate budgetary consequences of predictive genetic risk classification for statutory health insurance in Germany. Methods: A Markov model was developed in the form of a cohort simulation. It analyzes a population of female relatives of hereditary breast cancer patients. Mutation carriers are offered intensified screening, women with a BRCA1 or BRCA2 mutation can decide on prophylactic mastectomy and/or ovarectomy. The model considers the following scenarios: (a) steady demand for predictive genetic testing, and (b) rising demand. Most input parameters are based on data of the German Consortium for Hereditary Breast and Ovarian Cancer. The model contains 49 health states, starts in 2015, and runs for 10 years. Prices were evaluated from the perspective of statutory health insurance. Results: Steady demand leads to an expenditure of \text€49.8 million during the 10-year period. Rising demands lead to additional expenses of \text€125.5 million. The model reveals the genetic analysis to be the main cost driver while cost savings in treatment costs of breast and ovarian cancer are indicated. Conclusions: The results contribute to close the knowledge gap concerning the budgetary consequences due to genetic risk classification. A rising demand leads to additional costs especially due to costs for genetic analysis. The model indicates budget shifts with cost savings due to breast and ovarian cancer treatment in the scenario of rising demands.

Authors: Silke Neusser, Beate Lux, Cordula Barth, Kathrin Pahmeier, Kerstin Rhiem, Rita Schmutzler, Christoph Engel, Jürgen Wasem, Stefan Huster, Peter Dabrock, Anja Neumann

Date Published: 2nd Dec 2019

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

The GPRC5A frameshift variant c.183del is not associated with increased breast cancer risk in BRCA1 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract

Not specified

Authors: Kristina Klaschik, Jan Hauke, Guido Neidhardt, Christian Tränkle, Harald M. Surowy, Stefanie Heilmann-Heimbach, Gunter Rappl, Elisabeth Mangold, Norbert Arnold, Dieter Niederacher, Christian Sutter, Barbara Burwinkel, Christoph Engel, Barbara Wappenschmidt, Alfons Meindl, Corinna Ernst, Konstantin Weber-Lassalle, Nana Weber-Lassalle, Sandra Schmidt, Julika Borde, Rita K. Schmutzler, Eric Hahnen, Esther Pohl-Rescigno

Date Published: 4th Jan 2019

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective …e studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and \geq4 FTPs, respectively, Ptrend \textless .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Authors: Mary Beth Terry, Yuyan Liao, Karin Kast, Antonis C. Antoniou, Jasmine A. McDonald, Thea M. Mooij, Christoph Engel, Catherine Nogues, Bruno Buecher, Véronique Mari, Jessica Moretta-Serra, Laurence Gladieff, Elisabeth Luporsi, Daniel Barrowdale, Debra Frost, Alex Henderson, Carole Brewer, D. Gareth Evans, Diana Eccles, Jackie Cook, Kai-Ren Ong, Louise Izatt, Munaza Ahmed, Patrick J. Morrison, Charlotte J. Dommering, Jan C. Oosterwijk, Margreet G. E. M. Ausems, Mieke Kriege, Saundra S. Buys, Irene L. Andrulis, Esther M. John, Mary Daly, Michael Friedlander, Sue Anne McLachlan, Ana Osorio, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Yen Tan, Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-José Roos-Blom, Brita Arver, Håkan Olsson, Rita K. Schmutzler, John L. Hopper, Flora E. van Leeuwen, David Goldgar, Roger L. Milne, Douglas F. Easton, Matti A. Rookus, Nadine Andrieu

Date Published: 1st Oct 2018

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

INTRODUCTION While it has been reported that the risk of contralateral breast cancer in patients from BRCA1 or BRCA2 positive families is elevated, little is known about contralateral breast cancer …r risk in patients from high risk families that tested negative for BRCA1/2 mutations. METHODS A retrospective, multicenter cohort study was performed from 1996 to 2011 and comprised 6,235 women with unilateral breast cancer from 6,230 high risk families that had tested positive for BRCA1 (n = 1,154) or BRCA2 (n = 575) mutations or tested negative (n = 4,501). Cumulative contralateral breast cancer risks were calculated using the Kaplan-Meier product-limit method and were compared between groups using the log-rank test. Cox regression analysis was applied to assess the impact of the age at first breast cancer and the familial history stratified by mutation status. RESULTS The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 44.1% (95%CI, 37.6% to 50.6%) for patients from BRCA1 positive families, 33.5% (95%CI, 22.4% to 44.7%) for patients from BRCA2 positive families and 17.2% (95%CI, 14.5% to 19.9%) for patients from families that tested negative for BRCA1/2 mutations. Younger age at first breast cancer was associated with a higher risk of contralateral breast cancer. For women who had their first breast cancer before the age of 40 years, the cumulative risk of contralateral breast cancer after 25 years was 55.1% for BRCA1, 38.4% for BRCA2, and 28.4% for patients from BRCA1/2 negative families. If the first breast cancer was diagnosed at the age of 50 or later, 25-year cumulative risks were 21.6% for BRCA1, 15.5% for BRCA2, and 12.9% for BRCA1/2 negative families. CONCLUSIONS Contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations is similar to the risk in patients with sporadic breast cancer. Thus, the mutation status should guide decision making for contralateral mastectomy.

Authors: Kerstin Rhiem, Christoph Engel, Monika Graeser, Silke Zachariae, Karin Kast, Marion Kiechle, Nina Ditsch, Wolfgang Janni, Christoph Mundhenke, Michael Golatta, Dominic Varga, Sabine Preisler-Adams, Tilman Heinrich, Ulrich Bick, Dorothea Gadzicki, Susanne Briest, Alfons Meindl, Rita K. Schmutzler

Date Published: 1st Dec 2012

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

The TP53 Arg72Pro and MDM2 309GT polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. …. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T\textgreaterG, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. METHODS To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T\textgreaterG SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. RESULTS No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93-1.10, P(trend)=0.77; MDM2: HR=0.96, 95%CI: 0.84-1.09, P(trend)=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87-1.12, P(trend)=0.83; MDM2: HR=0.98, 95%CI: 0.80-1.21, P(trend)=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. CONCLUSION There was no evidence that TP53 Arg72Pro or MDM2 309T\textgreaterG, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.

Authors: O. M. Sinilnikova, A. C. Antoniou, J. Simard, S. Healey, M. Léoné, D. Sinnett, A. B. Spurdle, J. Beesley, X. Chen, M. H. Greene, J. T. Loud, F. Lejbkowicz, G. Rennert, S. Dishon, I. L. Andrulis, S. M. Domchek, K. L. Nathanson, S. Manoukian, P. Radice, I. Konstantopoulou, I. Blanco, A. L. Laborde, M. Durán, A. Osorio, J. Benitez, U. Hamann, F. B. L. Hogervorst, T. A. M. van Os, H. J. P. Gille, S. Peock, M. Cook, C. Luccarini, D. G. Evans, F. Lalloo, R. Eeles, G. Pichert, R. Davidson, T. Cole, J. Cook, J. Paterson, C. Brewer, D. J. Hughes, I. Coupier, S. Giraud, F. Coulet, C. Colas, F. Soubrier, E. Rouleau, I. Bièche, R. Lidereau, L. Demange, C. Nogues, H. T. Lynch, R. K. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Arnold, C. Sutter, H. Deissler, D. Schaefer, U. G. Froster, K. Aittomäki, H. Nevanlinna, L. McGuffog, D. F. Easton, G. Chenevix-Trench, D. Stoppa-Lyonnet

Date Published: 1st Oct 2009

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but … analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.

Authors: Helian Feng, Alexander Gusev, Bogdan Pasaniuc, Lang Wu, Jirong Long, Zomoroda Abu-Full, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Adalgeir Arason, Volker Arndt, Kristan J. Aronson, Banu K. Arun, Ella Asseryanis, Paul L. Auer, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel R. Barnes, Daniel Barrowdale, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna Białkowska, Ana Blanco, Carl Blomqvist, Bram Boeckx, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Qiuyin Cai, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Sander Canisius, Daniele Campa, Brian D. Carter, Jonathan Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Hans Christiansen, Wendy K. Chung, Kathleen B. M. Claes, Christine L. Clarke, Fergus J. Couch, Angela Cox, Simon S. Cross, Cezary Cybulski, Kamila Czene, Mary B. Daly, Miguel de La Hoya, Kim de Leeneer, Joe Dennis, Peter Devilee, Orland Diez, Susan M. Domchek, Thilo Dörk, Isabel Dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Bent Ejlertsen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson, Patricia A. Ganz, Susan M. Gapstur, Judy Garber, Montserrat García-Closas, José A. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Mark H. Greene, Jacek Gronwald, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Christopher Hake, Wei He, Jane Heyworth, Frans B. L. Hogervorst, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Guanmengqian Huang, Peter J. Hulick, Keith Humphreys, Evgeny N. Imyanitov, Claudine Isaacs, Milena Jakimovska, Anna Jakubowska, Paul James, Ramunas Janavicius, Rachel C. Jankowitz, Esther M. John, Nichola Johnson, Vijai Joseph, Audrey Jung, Beth Y. Karlan, Elza Khusnutdinova, Johanna I. Kiiski, Irene Konstantopoulou, Vessela N. Kristensen, Yael Laitman, Diether Lambrechts, Conxi Lazaro, Dominique Leroux, Goska Leslie, Jenny Lester, Fabienne Lesueur, Noralane Lindor, Sara Lindström, Wing-Yee Lo, Jennifer T. Loud, Jan Lubiński, Enes Makalic, Arto Mannermaa, Mehdi Manoochehri, Siranoush Manoukian, Sara Margolin, John W. M. Martens, Maria E. Martinez, Laura Matricardi, Tabea Maurer, Dimitrios Mavroudis, Lesley McGuffog, Alfons Meindl, Usha Menon, Kyriaki Michailidou, Pooja M. Kapoor, Austin Miller, Marco Montagna, Fernando Moreno, Lidia Moserle, Anna M. Mulligan, Taru A. Muranen, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Ines Nevelsteen, Finn C. Nielsen, Liene Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Håkan Olsson, Ana Osorio, Janos Papp, Tjoung-Won Park-Simon, Michael T. Parsons, Inge S. Pedersen, Ana Peixoto, Paolo Peterlongo, Julian Peto, Paul D. P. Pharoah, Kelly-Anne Phillips, Dijana Plaseska-Karanfilska, Bruce Poppe, Nisha Pradhan, Karolina Prajzendanc, Nadege Presneau, Kevin Punie, Katri Pylkäs, Paolo Radice, Johanna Rantala, Muhammad Usman Rashid, Gad Rennert, Harvey A. Risch, Mark Robson, Atocha Romero, Emmanouil Saloustros, Dale P. Sandler, Catarina Santos, Elinor J. Sawyer, Marjanka K. Schmidt, Daniel F. Schmidt, Rita K. Schmutzler, Minouk J. Schoemaker, Rodney J. Scott, Priyanka Sharma, Xiao-Ou Shu, Jacques Simard, Christian F. Singer, Anne-Bine Skytte, Penny Soucy, Melissa C. Southey, John J. Spinelli, Amanda B. Spurdle, Jennifer Stone, Anthony J. Swerdlow, William J. Tapper, Jack A. Taylor, Manuel R. Teixeira, Mary Beth Terry, Alex Teulé, Mads Thomassen, Kathrin Thöne, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Rob A. E. M. Tollenaar, Diana Torres, Thérèse Truong, Nadine Tung, Celine M. Vachon, Christi J. van Asperen, Ans M. W. van den Ouweland, Elizabeth J. van Rensburg, Ana Vega, Alessandra Viel, Paula Vieiro-Balo, Qin Wang, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Robert Winqvist, Xiaohong R. Yang, Drakoulis Yannoukakos, Argyrios Ziogas, Roger L. Milne, Douglas F. Easton, Georgia Chenevix-Trench, Wei Zheng, Peter Kraft, Xia Jiang

Date Published: 1st Jul 2020

Publication Type: Journal article

Human Diseases: breast cancer

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