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Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Purpose - This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. - Methods - The Prospective Lynch Syndrome Database (PLSD) was used to inves...

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Main Authors: Seppälä, Toni T. (Author) , Dominguez-Valentin, Mev (Author) , Crosbie, Emma J. (Author) , Engel, Christoph (Author) , Aretz, Stefan (Author) , Macrae, Finlay (Author) , Winship, Ingrid (Author) , Capella, Gabriel (Author) , Thomas, Huw (Author) , Hovig, Eivind (Author) , Nielsen, Maartje (Author) , Sijmons, Rolf H. (Author) , Bertario, Lucio (Author) , Bonanni, Bernardo (Author) , Tibiletti, Maria G. (Author) , Cavestro, Giulia M. (Author) , Mints, Miriam (Author) , Gluck, Nathan (Author) , Katz, Lior (Author) , Heinimann, Karl (Author) , Vaccaro, Carlos A. (Author) , Green, Kate (Author) , Lalloo, Fiona (Author) , Hill, James (Author) , Schmiegel, Wolff (Author) , Vangala, Deepak (Author) , Perne, Claudia (Author) , Strauß, Hans-Georg (Author) , Tecklenburg, Johanna (Author) , Holinski-Feder, Elke (Author) , Steinke-Lange, Verena (Author) , Mecklin, Jukka-Pekka (Author) , Plazzer, John-Paul (Author) , Pineda, Marta (Author) , Navarro, Matilde (Author) , Vida, Joan B. (Author) , Kariv, Revital (Author) , Rosner, Guy (Author) , Piñero, Tamara A. (Author) , Pavicic, Walter (Author) , Kalfayan, Pablo (Author) , Ten Broeke, Sanne W. (Author) , Jenkins, Mark A. (Author) , Sunde, Lone (Author) , Bernstein, Inge (Author) , Burn, John (Author) , Greenblatt, Marc (Author) , de Vos tot Nederveen Cappel, Wouter H. (Author) , Della Valle, Adriana (Author) , Lopez-Koestner, Francisco (Author) , Alvarez, Karin (Author) , Büttner, Reinhard (Author) , Görgens, Heike (Author) , Morak, Monika (Author) , Holzapfel, Stefanie (Author) , Hüneburg, Robert (Author) , Knebel Doeberitz, Magnus von (Author) , Loeffler, Markus (Author) , Redler, Silke (Author) , Weitz, Jürgen (Author) , Pylvänäinen, Kirsi (Author) , Renkonen-Sinisalo, Laura (Author) , Lepistö, Anna (Author) , Hopper, John L. (Author) , Win, Aung K. (Author) , Lindor, Noralane M. (Author) , Gallinger, Steven (Author) , Le Marchand, Loïc (Author) , Newcomb, Polly A. (Author) , Figueiredo, Jane C. (Author) , Thibodeau, Stephen N. (Author) , Therkildsen, Christina (Author) , Wadt, Karin A. W. (Author) , Mourits, Marian J. E. (Author) , Ketabi, Zohreh (Author) , Denton, Oliver G. (Author) , Rødland, Einar A. (Author) , Vasen, Hans (Author) , Neffa, Florencia (Author) , Esperon, Patricia (Author) , Tjandra, Douglas (Author) , Möslein, Gabriela (Author) , Rokkones, Erik (Author) , Sampson, Julian R. (Author) , Evans, D. G. (Author) , Møller, Pål (Author)
Format: Article (Journal)
Language:English
Published: 17 March 2021
In: European journal of cancer
Year: 2021, Volume: 148, Pages: 124-133
ISSN:1879-0852
DOI:10.1016/j.ejca.2021.02.022
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejca.2021.02.022
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804921001052
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Author Notes:Toni T. Seppälä, Mev Dominguez-Valentin, Emma J. Crosbie, Christoph Engel, Stefan Aretz, Finlay Macrae, Ingrid Winship, Gabriel Capella, Huw Thomas, Eivind Hovig, Maartje Nielsen, Rolf H. Sijmons, Lucio Bertario, Bernardo Bonanni, Maria G. Tibiletti, Giulia M. Cavestro, Miriam Mints, Nathan Gluck, Lior Katz, Karl Heinimann, Carlos A. Vaccaro, Kate Green, Fiona Lalloo, James Hill, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Hans-Georg Strauß, Johanna Tecklenburg, Elke Holinski-Feder, Verena Steinke-Lange, Jukka-Pekka Mecklin, John-Paul Plazzer, Marta Pineda, Matilde Navarro, Joan B. Vida, Revital Kariv, Guy Rosner, Tamara A. Piñero, Walter Pavicic, Pablo Kalfayan, Sanne W. ten Broeke, Mark A. Jenkins, Lone Sunde, Inge Bernstein, John Burn, Marc Greenblatt, Wouter H. de Vos tot Nederveen Cappel, Adriana Della Valle, Francisco Lopez-Koestner, Karin Alvarez, Reinhard Büttner, Heike Görgens, Monika Morak, Stefanie Holzapfel, Robert Hüneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Silke Redler, Jürgen Weitz, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepistö, John L. Hopper, Aung K. Win, Noralane M. Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Christina Therkildsen, Karin A.W. Wadt, Marian J.E. Mourits, Zohreh Ketabi, Oliver G. Denton, Einar A. Rødland, Hans Vasen, Florencia Neffa, Patricia Esperon, Douglas Tjandra, Gabriela Möslein, Erik Rokkones, Julian R. Sampson, D.G. Evans, Pål Møller

MARC

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245 1 0 |a Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants  |b a Prospective Lynch Syndrome Database report  |c Toni T. Seppälä, Mev Dominguez-Valentin, Emma J. Crosbie, Christoph Engel, Stefan Aretz, Finlay Macrae, Ingrid Winship, Gabriel Capella, Huw Thomas, Eivind Hovig, Maartje Nielsen, Rolf H. Sijmons, Lucio Bertario, Bernardo Bonanni, Maria G. Tibiletti, Giulia M. Cavestro, Miriam Mints, Nathan Gluck, Lior Katz, Karl Heinimann, Carlos A. Vaccaro, Kate Green, Fiona Lalloo, James Hill, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Hans-Georg Strauß, Johanna Tecklenburg, Elke Holinski-Feder, Verena Steinke-Lange, Jukka-Pekka Mecklin, John-Paul Plazzer, Marta Pineda, Matilde Navarro, Joan B. Vida, Revital Kariv, Guy Rosner, Tamara A. Piñero, Walter Pavicic, Pablo Kalfayan, Sanne W. ten Broeke, Mark A. Jenkins, Lone Sunde, Inge Bernstein, John Burn, Marc Greenblatt, Wouter H. de Vos tot Nederveen Cappel, Adriana Della Valle, Francisco Lopez-Koestner, Karin Alvarez, Reinhard Büttner, Heike Görgens, Monika Morak, Stefanie Holzapfel, Robert Hüneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Silke Redler, Jürgen Weitz, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepistö, John L. Hopper, Aung K. Win, Noralane M. Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Christina Therkildsen, Karin A.W. Wadt, Marian J.E. Mourits, Zohreh Ketabi, Oliver G. Denton, Einar A. Rødland, Hans Vasen, Florencia Neffa, Patricia Esperon, Douglas Tjandra, Gabriela Möslein, Erik Rokkones, Julian R. Sampson, D.G. Evans, Pål Møller 
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520 |a Purpose - This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. - Methods - The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years. - Results - Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery. - Conclusion - Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes. 
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