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1. Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome

Author

Ana Beatriz Sánchez-Heras, Estela Dámaso, Adela Castillejo, Mercedes Robledo, Alexandre Teulé, Conxi Lázaro, Rosario Sánchez-Martínez, Ángel Zúñiga, Adrià López-Fernández, Judith Balmaña, Luis Robles, Teresa Ramon y Cajal, M. Isabel Castillejo, Raquel Perea Ibañez, Carmen Martínez Sevila, Andrea Sánchez-Mira, Inés Escandell, Luís Gómez, Pere Berbel, and José Luis Soto

Subjects
Haplotypes, Founder mutation, Common ancestor, Hereditary leiomyomatosis, FH, Renal cell cancer, Medicine
Abstract

Abstract Background Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. Results Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61–0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12–26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. Conclusions In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing.

Published
2024
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2. SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population.

Author

José Marcos Moreno-Cabrera, Lidia Feliubadaló, Marta Pineda, Patricia Prada-Dacasa, Mireia Ramos-Muntada, Jesús del Valle, Joan Brunet, Bernat Gel, María Currás-Freixes, Bruna Calsina, Milton E. Salazar-Hidalgo, Marta Rodríguez-Balada, Bàrbara Roig, Sara Fernández-Castillejo, Mercedes Durán Domínguez, Mónica Arranz Ledo, Mar Infante Sanz, Adela Castillejo, Estela Dámaso, José L. Soto, Montserrat de Miguel, Beatriz Hidalgo Calero, José M. Sánchez-Zapardiel, Teresa Ramon y Cajal, Adriana Lasa, Alexandra Gisbert-Beamud, Anael López-Novo, Clara Ruiz-Ponte, Miriam Potrony, María I álvarez-Mora, Ana Osorio, Isabel Lorda-Sánchez, Mercedes Robledo, Alberto Cascón, Anna Ruiz, Nino Spataro, Imma Hernan, Emma Borràs, Alejandro Moles-Fernández, Julie Earl, Juan Cadiñanos, Ana B. Sánchez-Heras, Anna Bigas, Gabriel Capellá, and Conxi Lázaro

Published
2024
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3. A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants

Author

Julie Earl, Cristina Galindo-Pumariño, Jessica Encinas, Emma Barreto, Maria E. Castillo, Vanessa Pachón, Reyes Ferreiro, Mercedes Rodríguez-Garrote, Silvia González-Martínez, Teresa Ramon y Cajal, Luis Robles Diaz, Isabel Chirivella-Gonzalez, Montse Rodriguez, Eva Martínez de Castro, David García-Seisdedos, Gloria Muñoz, Juan Manuel Rosa Rosa, Mirari Marquez, Nuría Malats, and Alfredo Carrato

Subjects
Medicine, Medicine (General), R5-920
Abstract

Background: The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two affected first degree relatives, with an estimated incidence of 4%–10%. The genetic basis is unknown in the majority of families although around 10%–13% of families carry germline mutations in known genes associated with hereditary cancer and pancreatitis syndromes. Methods: Panel sequencing was performed of 35 genes associated with hereditary cancer in 43 PDAC cases from families with an apparent hereditary pancreatic cancer syndrome. Findings: Pathogenic variants were identified in 19% (5/26) of PDAC cases from pure FPC families in the genes MLH1, CDKN2A, POLQ and FANCM. Low frequency potentially pathogenic VUS were also identified in 35% (9/26) of PDAC cases from FPC families in the genes FANCC, MLH1, PMS2, CFTR, APC and MUTYH. Furthermore, an important proportion of PDAC cases harboured more than one pathogenic, likely pathogenic or potentially pathogenic VUS, highlighting the multigene phenotype of FPC. Interpretation: The genetic basis of familial or hereditary pancreatic cancer can be explained in 21% of families by previously described hereditary cancer genes. Low frequency variants in other DNA repair genes are also present in 35% of families which may contribute to the risk of pancreatic cancer development. Funding: This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Temática de investigación cooperativa en cáncer: RTICC (RD12/0036/0073) and La Asociación Española contra el Cáncer: AECC (Grupos Coordinados Estables 2016). Keywords: Familial pancreatic cancer, Panel sequencing, DNA repair and hereditary cancer genes, Pathogenic variants

Published
2020
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4. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author

Koroveshi, Dhurata, Bouzid, Kamel, Casalnuovo, Monica, Cascallar, Diana, Korbenfeld, Ernesto Pablo, Bastick, Patricia, Beith, Jane, Colosimo, Maree, Friedlander, Michael, Ganju, Vinod, Green, Michael, Patterson, Kevin, Redfern, Andrew, Richardson, Gary, Ceric, Timur, Gordana, Kecman, Beato, Carlos Augusto, Ferrari, Marcela, Hegg, Roberto, Helena, Vanessa, Ismael, Gustavo Fernando, Lessa, Alvaro Edson, Mano, Max, Morelle, Alessandra, Nogueira, Jose Alberto, Timcheva, Konstanta, Tomova, Antoaneta, Tsakova, Maya, Zlatareva-Petrova, Ani, Asselah, Jamil, Assi, Hazem, Brezden-Masley, Christine, Chia, Stephen, Freedman, Ori, Harb, Mohammed, Joy, Anil Abraham, Kulkarni, Swati, Prady, Catherine, Gaete, Alejandro Andres Acevedo, Matamala, Luis, Torres, Roberto, Yanez, Eduardo, Franco, Sandra, Urrego, Marcela, Gugić, Damir, Vrbanec, Damir, Melichar, Bohuslav, Prausová, Jana, Vyzula, Rostislav, Pilarte, Rafael Gutierrez, León, María Isabel, Muñoz, Rene, Ramos, Glenda, Azeem, Hamdy Abdel, Aziz, Amr Abdel, El Zawahry, Heba, Osegueda, Finlander Rosales, Alexandre, Jerome, Artignan, Xavier, Barletta, Hugues, Beguier, Emmanuel, Berdah, Jean-François, Marty, Chantal Bernard, Bollet, Marc, Bourgeois, Hugues, Bressac, Claude, Burki, Franck, Campone, Mario, Coeffic, David, Cojocarasu, Oana Zveltlana, Dagada, Corinne, Dalenc, Florence, Del Piano, Francesco, Desauw, Christophe, Desmoulins, Isabelle, Dohollou, Nadine, Egreteau, Joelle, Ferrero, Jean-Marc, Foa, Cyril, Garidi, Reda, Gasnault, Laurent, Gligorov, Joseph, Guardiola, Emmanuel, Hamizi, Salima, Jarcau, Rosana, Jacquin, Jean-Philippe, Jaubert, Dominique, Jolimoy, Geneviève, Mineur, Hortense Laharie, Largillier, Remy, Leduc, Bernard, Martin, Philippe, Melis, Adrien, Monge, Jeremy, Moullet, Isabelle, Mousseau, Mireille, Nguyen, Suzanne, Orfeuvre, Hubert, Petit, Thierry, Pivot, Xavier, Priou, Frank, Bach, Isabelle Sillet, Simon, Helene, Stefani, Laetitia, Uwer, Lionel, Youssef, Ali, Aktas, Bahriye, von der Assen, Albert, Augustin, Doris, Balser, Christina, Bauer, Lelia-Eveline, Bechtner, Christina, Beyer, Greta, Brucker, Cosima, Bückner, Ute, Busch, Steffi, Christensen, Bernd, Deryal, Mustafa, Farrokh, Andre, Faust, Elke, Friedrichs, Kay, Graf, Heiko, Griesshammer, Martin, Grischke, Eva-Maria, Hänle, Claudia, Heider, Andrea, Henschen, Stephan, Hesse, Tobias, Jackisch, Christian, Kisro, Jens, Köhler, Andreas, Kuemmel, Sherko, Lampe, Dieter, Lantzsch, Tilmann, Latos, Kunibert, Lex, Benno, Liedtke, Cornelia, Luedders, Doerte, Maintz, Christoph, Müller, Volkmar, Overkamp, Friedrich, Park-Simon, Tjoung-won, Paul, Marion, Prechtl, Anita, Ringsdorf, Uta, Runnebaum, Ingo, Ruth, Sylvia, Salat, Christoph, Scheffen, Iris, Schilling, Jörg, Schmatloch, Sabine, Schmidt, Marcus, Schneeweiss, Andreas, Schrader, Iris, Seipelt, Gernot, Simon, Elke, Stefek, Andrea, Stickeler, Elmar, Thill, Marc, Tio, Joke, Tuczek, Anna, Warm, Mathias, Weigel, Michael, Wischnik, Arthur, Wojcinski, Sebastian, Ziegler-Löhr, Katja, Aravantinos, Gerasimos, Ardavanis, Alexandros, Fountzilas, George, Gogas, Helen, Kakolyris, Stylianos, Mavroudis, Dimitris, Papadimitriou, Christos, Papandreou, Christos, Papazisis, Konstantinos, Castro, Hugo, Hernandez-Monroy, Cesar Estuardo, Ngan, Roger, Yeo, Winnie, Bittner, Nora, Boer, Katalin, Csejtei, Andras, Horvath, Zsolt, Kocsis, Judit, Mangel, László Csaba, Mezei, Klara, Nagy, Zsuzsanna, Szanto, Janos, Atmakusuma, Djumhana, Fadjari, Heri, Kurnianda, Djohan, Prayogo, Nugroho, Tanggo, Eddie Herman, Coate, Linda, Hennessy, Bryan, Kelly, Cathy, Martin, Michael, Nasim, Saira, O'Connor, Miriam, Aieta, Michele, Allegrini, Giacomo, Amadori, Dino, Bidoli, Paolo, Biti, Giampaolo, Bordonaro, Roberto, Bottini, Alberto, Carterni, Giacomo, Cavanna, Luigi, Cazzaniga, Marina, Cognetti, Francesco, Contu, Antonio, Cruciani, Giorgio, Donadio, Michela, Falcone, Alfredo, Farci, Daniele, Forcignanò, R. Chiara, Frassoldati, Antonio, Gaion, Fernando, Gamucci, Teresa, Giotta, Francesco, de Laurentiis, Michele, Livi, Lorenzo, Lorusso, Vito, Maiello, Evaristo, Marchetti, Paolo, Mariani, Gabriella, Mion, Marta, Moscetti, Luca, Musolino, Antonino, Pazzola, Antonio, Pedrazzoli, Paolo, Pigi, Andrea, de Placido, Sabino, Caremoli, Elena Rota, Santoro, Armando, Tienghi, Amelia, Ahn, Jin-Seok, Jung, Kyung Hae, Lee, Keun Seok, Lee, Soo Hyeon, Seo, Jae Hong, Sohn, Joo-Hyuk, Cesas, Alvydas, Juozaityte, Elona, Cheah, Nellie Lay Chin, Chong, Flora Li Tze, Devi, Beena C.R., Phua, Vincent, Teoh, Darren, Ching, Lee Wei, Yusof, Mastura, Corona, Jorge, Dominguez, Adriana, Mendoza, René Lazaro González, Hernandez, Carlos Alberto, Ramiro, Alejandro Juarez, Santos, Juan Matos, Espinosa, Paola Morales, Villarreal Garza, Cynthia Mayte, Errihani, Hassan, Bakker, Sandra, van den Berkmortel, Franchette, Blaisse, R.J.B., Huinink, Daan ten Bokkel, van den Bosch, J., Braun, J.J., Dercksen, M.W., Droogendijk, Helga, Erdkamp, Frans, Haringhuizen, Annebeth, de Jongh, F.E., Kok, T.C., Los, Maartje, Madretsma, Stanley, Terwogt, Jetske M. Meerum, van der Padt, Annemieke, van Rossum-Schornagel, Quirine Clementine, Smilde, T.J., de Valk, Bart, van der Velden, Annette, van Warmerdam, Laurence, van de Wouw, A.J., North, Richard, Kersten, Christian, Mjaaland, Ingvild, Wist, Erik, Aziz, Zeba, Masood, Nehal, Rashid, Kamran, Shah, Mazhar, Alcedo, Juan Carlos, Aleman, Diana, Neciosup, Silvia, Reategui, Rocio, Valdiviezo, Natalia, Vera, Luis, Fernando, Gracieux, Roque, Fernando, Strebel, Heinrik Martin, Krzemieniecki, Krzysztof, Litwiniuk, Maria, Mruk, Andrzej, Pienkowski, Tadeusz, Sawrycki, Piotr, Slomian, Grzegorz, Tomczak, Piotr, Afonso, Noemia, Cardoso, Fátima, Damasceno, Margarida, Nave, Monica, Badulescu, Florinel, Ciule, Larisa, Curescu, Stefan, Eniu, Alexandru, Filip, Dumitru, Grecea, Daniela, Jinga, Dan-Corneliu, Lungulescu, Dan, Oprean, Cristina Marinela, Stanculeanu, Dana Lucia, Turdean, Maria, Dvornichenko, Viktoria, Emelyanov, Sergey, Lichinitser, Mikhail, Manikhas, Alexey, Sakaeva, Dina, Shirinkin, Vadim, Stroyakovskiy, Daniil, Abulkhair, Omalkhair, Zekri, Jamal, Filipovic, Sladjana, Kovcin, Vladimir, Nedovic, Jasmina, Pesic, Jasna, Vasovic, Suzana, Ng, Raymond, Bystricky, Branislav, Leskova, Jaroslava, Mardiak, Jozef, Mišurová, Etela, Wagnerova, Maria, Takač, Iztok, Demetriou, Georgia Savva, Dreosti, Lydia, Govender, Poovandren, Jordaan, Johannes Petrus, Veersamy, Petrosian, Romero, Jose Luis Alonso, Lopez, Norberto Batista, Arias, Carmen Cañabate, Chacon, Jose, Aramburo, Antonio Fernandez, Morales, Luis Antonio Fernandez, Garcia, Mirta, Estevez, Laura Garcia, Garcia-Palomo Perez, Andres, Garcia Saenz, Jose Angel, Garcia Sanchis, Laura, Cubells, Laia Garrigos, Cortijo, Lucia Gonzalez, Santiago, Santiago Gonzalez, De Aranguiz, Blanca Hernando Fernandez, Mañas, José Juan Illarramendi, Gallego, Pedro Jimenez, Cussac, Antonio Llombart, Ferrandiz, Cristina Llorca, Garrido, Maria Lomas, Alvarez, Pilar Lopez, Vega, Jose Manuel Lopez, Del Prado, Purificacion Martinez, Jañez, Noelia Martinez, Murillo, Serafin Morales, Rosales, Adolfo Murias, Jaso, Laura Murillo, Fernandez, Ignacio Pelaez, Martorell, Antonia Perello, Carrion, Ramon Perez, Simon, Sonia Pernas, Alcibar, Arrate Plazaola, Lorenzo, Jose Ponce, Garcia, Vanesa Quiroga, Asensio, Teresa Ramon y Cajal, Maicas, Maria Dolores Torregrosa, Villanueva Silva, Maria Jose, Killander, Fredrika, Svensson, Jan Henry, Fehr, Mathias, Hauser, Nik, Müller, Andreas, Pagani, Olivia, Passmann-Kegel, Heike, Popescu, Razvan, Rabaglio, Manuela, Rauch, Daniel, Schlatter, Christina, Zaman, Khalil, Chang, Tsai-Wang, Huang, Chiun-Sheng, Wang, Hwei-Chung, Yu, Jyh-Cherng, Bandidwattanawong, Chanyoot, Maneechavakajorn, Jedzada, Seetalarom, Kasan, Dejthevaporn, Thitiya (Sirisinha), Somwangprasert, Areewan, Vongsaisuwon, Mawin, Akbulut, Hakan, Altundag, Kadri, Arican, Ali, Bozcuk, Hakan, Eralp, Yesim, Idris, Mohamed, Isikdogan, Abdurrahman, Senol, Coskun Hasan, Sevinc, Alper, Uygun, Kazim, Yucel, Eftal, Yucel, Idris, Yumuk, Fulden, Shparyk, Yaroslav, Voitko, Nataliia, Jaloudi, Mohammed, Adams, Jocelyn, Agrawal, Rajiv, Ahmed, Samreen, Alhasso, Abdulla, Allerton, Rozenn, Anwar, Suhail, Archer, Caroline, Ashford, Richard, Barraclough, Lisa, Bertelli, Gianfilippo, Bishop, Jill, Branson, Tony, Butt, Mohammed, Chakrabarti, Amit, Chakraborti, Prabir, Churn, Mark, Crowley, Clare, Davis, Ruth, Dhadda, Amandeep, Eldeeb, Hany, Fraser, Judith, Hall, Julia, Hickish, Tamas, Hogg, Martin, Howe, Theresa, Joffe, Jonathan, Kelleher, Muireann, Kelly, Stephen, Kendall, Anne, Kristeleit, Hartmut, Lumsden, Graeme, Macmillan, Craig, MacPherson, Iain, Malik, Zafar, Mithal, Natasha, Neal, Anthony, Panwar, Udaiveer, Proctor, Andrew, Proctor, Steven John, Raj, Sanjay, Rehman, Shazza, Sandri, Ines, Scatchard, Kate, Sherwin, Elizabeth, Sims, Eliot, Singer, Julian, Smith, Sarah, Tahir, Saad, Taylor, Wendy, Tsalic, Medy, Verrill, Mark, Wardley, Andrew, Waters, Simon, Wheatley, Duncan, Wright, Kathryn, Yuille, Frances, Alonso, Isabel, Artagaveytia, Nora, Rodriguez, Robinson, Arbona, Esther, Garcia, Yuraima, Lion, Lorena, Marcano, Dalila, Van Thuan, Tran, Gligorov, J., Ataseven, B., Verrill, M., De Laurentiis, M., Jung, K.H., Azim, H.A., Al-Sakaff, N., Lauer, S., Shing, M., and Pivot, X.

Published
2017
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5. Study protocol to assess the quality of life after preventive bilateral salpingo-oophorectomy in BRCA1/2 and PALB2 mutation carriers

Author

Blanc, Patricia Muro, primary, Verges, Nuria Calvo, additional, Ruiz, Rosa Alfonso, additional, Diaz, Javier Gavira, additional, Capó, Josep Perelló, additional, Moreno, Cristina Soler, additional, Negre, Ramon Rovira, additional, Asensio, Teresa Ramon y Cajal, additional, and Gasull, Misericordia Guinot, additional

Published
2023
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6. SEOM–GEICAM–SOLTI clinical guidelines in advanced breast cancer (2022)

Author

Jose Angel Garcia-Saenz, Isabel Blancas, Isabel Echavarria, Carmen Hinojo, Mireia Margeli, Fernando Moreno, Sonia Pernas, Teresa Ramon y Cajal, Nuria Ribelles, and Meritxell Bellet

Subjects
Endocrine therapy, IOT, Cancer Research, ADC, Oncology, Anti-HER2 therapy, Advanced breast cancer, General Medicine, Guidelines, ABC
Abstract

Advanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer.

Published
2023
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7. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author

Elizabeth K Bancroft, Elizabeth C Page, Mark N Brook, Sarah Thomas, Natalie Taylor, Jennifer Pope, Jana McHugh, Ann-Britt Jones, Questa Karlsson, Susan Merson, Kai Ren Ong, Jonathan Hoffman, Camilla Huber, Lovise Maehle, Eli Marie Grindedal, Astrid Stormorken, D Gareth Evans, Jeanette Rothwell, Fiona Lalloo, Angela F Brady, Marion Bartlett, Katie Snape, Helen Hanson, Paul James, Joanne McKinley, Lyon Mascarenhas, Sapna Syngal, Chinedu Ukaegbu, Lucy Side, Tessy Thomas, Julian Barwell, Manuel R Teixeira, Louise Izatt, Mohnish Suri, Finlay A Macrae, Nicola Poplawski, Rakefet Chen-Shtoyerman, Munaza Ahmed, Hannah Musgrave, Nicola Nicolai, Lynn Greenhalgh, Carole Brewer, Nicholas Pachter, Allan D Spigelman, Ashraf Azzabi, Brian T Helfand, Dorothy Halliday, Saundra Buys, Teresa Ramon y Cajal, Alan Donaldson, Kathleen A Cooney, Marion Harris, John McGrath, Rosemarie Davidson, Amy Taylor, Peter Cooke, Kathryn Myhill, Matthew Hogben, Neil K Aaronson, Audrey Ardern-Jones, Chris H Bangma, Elena Castro, David Dearnaley, Alexander Dias, Tim Dudderidge, Diana M Eccles, Kate Green, Jorunn Eyfjord, Alison Falconer, Christopher S Foster, Henrik Gronberg, Freddie C Hamdy, Oskar Johannsson, Vincent Khoo, Hans Lilja, Geoffrey J Lindeman, Jan Lubinski, Karol Axcrona, Christos Mikropoulos, Anita V Mitra, Clare Moynihan, Holly Ni Raghallaigh, Gad Rennert, Rebecca Collier, Judith Offman, Zsofia Kote-Jarai, Rosalind A Eeles, Lisa Adams, Julian Adlard, Rosa Alfonso, Saira Ali, Angela Andrew, Luís Araújo, Nazya Azam, Darran Ball, Queenstone Barker, Alon Basevitch, Barbara Benton, Cheryl Berlin, Nicola Bermingham, Leah Biller, Angela Bloss, Matilda Bradford, Nicola Bradshaw, Amy Branson, Charles Brendler, Maria Brennan, Barbara Bulman, Lucy Burgess, Declan Cahill, Alice Callard, Nuria Calvo Verges, Marta Cardoso, Vanda Carter, Mario Catanzaro, Anthony Chamberlain, Cyril Chapman, Michael Chong, Caroline Clark, Virginia Clowes, Lyn Cogley, Trevor Cole, Cecilia Compton, Tom Conner, Sandra Cookson, Philip Cornford, Philandra Costello, Laura Coulier, Michaela Davies, Christopher Dechet, Bianca DeSouza, Gemma Devlin, Fiona Douglas, Emma Douglas, Darshna Dudakia, Alexis Duncan, Natalie Ellery, Sarah Everest, Sue Freemantle, Mark Frydenberg, Debbie Fuller, Camila Gabriel, Madeline Gale, Lynda Garcia, Simona Gay, Elena Genova, Angela George, Demetra Georgiou, Alexandra Gisbert, Margaret Gleeson, Wayne Glover, Vincent Gnanapragasam, Sally Goff, David Goldgar, Nuno Gonçalves, Selina Goodman, Jennifer Gorrie, Hannah Gott, Anna Grant, Catherine Gray, Julie Griffiths, Karin Gupwell, Jana Gurasashvili, Eldbjørg Hanslien, Sigurdis Haraldsdottir, Rachel Hart, Catherine Hartigan, Lara Hawkes, Tricia Heaton, Alex Henderson, Rui Henrique, Kathrine Hilario, Kathryn Hill, Peter Hulick, Clare Hunt, Melanie Hutchings, Rita Ibitoye, Thomas Inglehearn, Joanna Ireland, Farah Islam, Siti Ismail, Chris Jacobs, Denzil James, Sharon Jenkins, Irene Jobson, Anne Johnstone, Oliver Jones, Sagi Josefsberg Ben-Yehoshua, Beckie Kaemba, Karen Kaul, Zoe Kemp, Netty Kinsella, Margaret Klehm, Roger Kockelbergh, Kelly Kohut, Monika Kosicka-Slawinska, Anjana Kulkarni, Pardeep Kumar, Jimmy Lam, Mandy LeButt, Dan Leibovici, Ramona Lim, Lauren Limb, Claire Lomas, Mark Longmuir, Consol López, Tiziana Magnani, Sofia Maia, Jessica Maiden, Alison Male, Merrie Manalo, Phoebe Martin, Donna McBride, Michael McGuire, Romayne McMahon, Claire McNally, Terri McVeigh, Ehud Melzer, Mark Mencias, Catherine Mercer, Gillian Mitchell, Josefina Mora, Catherine Morton, Cathryn Moss, Morgan Murphy, Declan Murphy, Shumi Mzazi, Maria Nadolski, Anna Newlin, Pedro Nogueira, Rachael O'Keefe, Karen O'Toole, Shona O'Connell, Chris Ogden, Linda Okoth, Jorge Oliveira, Edgar Paez, Joan Palou, Linda Park, Nafisa Patel, João Paulo Souto, Allison Pearce, Ana Peixoto, Kimberley Perez, Lara Petelin, Gabriella Pichert, Charlotte Poile, Alison Potter, Nadia Preitner, Helen Purnell, Ellen Quinn, Paolo Radice, Brigette Rankin, Katie Rees, Caroline Renton, Kate Richardson, Peter Risby, Jason Rogers, Maggie Ruderman, April Ruiz, Anaar Sajoo, Natale Salvatore, Victoria Sands, Francesco Sanguedolce, Ayisha Sattar, Kathryn Saunders, Lyn Schofield, Rodney Scott, Anne Searle, Ravinder Sehra, Christina Selkirk, Kylie Shackleton, Sue Shanley, Adam Shaw, Daniel Shevrin, Hannah Shipman, Zahirah Sidat, Kas Siguake, Kate Simon, Courtney Smyth, Lesley Snadden, Nita Solanky, Joyce Solomons, Margherita Sorrentino, Barbara Stayner, Robert Stephenson, Elena Stoffel, Maggie Thomas, Alan Thompson, Lizzie Tidey, Marc Tischkowitz, Audrey Torokwa, Sharron Townshend, Katy Treherne, Karen Tricker, Quoc-Dien Trinh, Vishakha Tripathi, Clare Turnbull, Riccardo Valdagni, Nicholas Van As, Vickie Venne, Lizzie Verdon, Marco Vitellaro, Kristen Vogel, Lisa Walker, Amy Watford, Cathy Watt, Ilana Weintroub, Shelly Weiss, Scott Weissman, Michelle Weston, Jennifer Wiggins, Gillian Wise, Christopher Woodhouse, Pembe Yesildag, Alice Youngs, Matthew Yurgelun, Fabiana Zollo, Urology, Brook, Mark N [0000-0002-8969-2378], and Apollo - University of Cambridge Repository

Subjects
Oncology, Adult, Male, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Heterozygote, Prostate biopsy, Urology, Prostate-Specific Antigen/blood, DNA Mismatch Repair/genetics, DNA Mismatch Repair, Prostate cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Biomarkers, Tumor, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, Prospective cohort study, Early Detection of Cancer, Germ-Line Mutation, Aged, Prostatic Neoplasms/diagnosis, medicine.diagnostic_test, business.industry, Endometrial cancer, Incidence, Cancer, Prostatic Neoplasms, Articles, Prostate-Specific Antigen, Middle Aged, medicine.disease, Lynch syndrome, digestive system diseases, DNA-Binding Proteins, Prostate cancer screening, MutS Homolog 2 Protein, MSH2, Biomarkers, Tumor/blood, population characteristics, business, human activities, geographic locations, DNA-Binding Proteins/genetics, MutS Homolog 2 Protein/genetics
Abstract

Funder: Victorian Cancer Agency, Funder: NIHR Manchester Biomedical Research Centre, Funder: Cancer Research UK, Funder: Cancer Council Tasmania, Funder: Instituto de Salud Carlos III, Funder: Cancer Australia, Funder: NIHR Oxford Biomedical Research Centre, Funder: Fundación Científica de la Asociación Española Contra el Cáncer, Funder: Cancer Council South Australia, Funder: Swedish Cancer Society, Funder: NIHR Cambridge Biomedical Research Centre, Funder: Institut Català de la Salut, Funder: Cancer Council Victoria, Funder: Prostate Cancer Foundation of Australia, Funder: National Institutes of Health, BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with ClinicalTrials.gov, NCT00261456, and is now closed to accrual. FINDINGS: Between Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1-2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3-7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0-2·6), MSH6 carriers was 3·0% (four of 135; 0·8-7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0-68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3-46·0). INTERPRETATION: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. FUNDING: Cancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer.

Published
2021
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8. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

Author

Elizabeth C, Page, Elizabeth K, Bancroft, Mark N, Brook, Melissa, Assel, Mona, Hassan Al Battat, Sarah, Thomas, Natalie, Taylor, Anthony, Chamberlain, Jennifer, Pope, Holly Ni, Raghallaigh, D Gareth, Evans, Jeanette, Rothwell, Lovise, Maehle, Eli Marie, Grindedal, Paul, James, Lyon, Mascarenhas, Joanne, McKinley, Lucy, Side, Tessy, Thomas, Christi, van Asperen, Hans, Vasen, Lambertus A, Kiemeney, Janneke, Ringelberg, Thomas Dyrsø, Jensen, Palle J S, Osther, Brian T, Helfand, Elena, Genova, Rogier A, Oldenburg, Cezary, Cybulski, Dominika, Wokolorczyk, Kai-Ren, Ong, Camilla, Huber, Jimmy, Lam, Louise, Taylor, Monica, Salinas, Lidia, Feliubadaló, Jan C, Oosterwijk, Wendy, van Zelst-Stams, Jackie, Cook, Derek J, Rosario, Susan, Domchek, Jacquelyn, Powers, Saundra, Buys, Karen, O'Toole, Margreet G E M, Ausems, Rita K, Schmutzler, Kerstin, Rhiem, Louise, Izatt, Vishakha, Tripathi, Manuel R, Teixeira, Marta, Cardoso, William D, Foulkes, Armen, Aprikian, Heleen, van Randeraad, Rosemarie, Davidson, Mark, Longmuir, Mariëlle W G, Ruijs, Apollonia T J M, Helderman van den Enden, Muriel, Adank, Rachel, Williams, Lesley, Andrews, Declan G, Murphy, Dorothy, Halliday, Lisa, Walker, Annelie, Liljegren, Stefan, Carlsson, Ashraf, Azzabi, Irene, Jobson, Catherine, Morton, Kylie, Shackleton, Katie, Snape, Helen, Hanson, Marion, Harris, Marc, Tischkowitz, Amy, Taylor, Judy, Kirk, Rachel, Susman, Rakefet, Chen-Shtoyerman, Allan, Spigelman, Nicholas, Pachter, Munaza, Ahmed, Teresa, Ramon Y Cajal, Janez, Zgajnar, Carole, Brewer, Neus, Gadea, Angela F, Brady, Theo, van Os, David, Gallagher, Oskar, Johannsson, Alan, Donaldson, Julian, Barwell, Nicola, Nicolai, Eitan, Friedman, Elias, Obeid, Lynn, Greenhalgh, Vedang, Murthy, Lucia, Copakova, Sibel, Saya, John, McGrath, Peter, Cooke, Karina, Rønlund, Kate, Richardson, Alex, Henderson, Soo H, Teo, Banu, Arun, Karin, Kast, Alexander, Dias, Neil K, Aaronson, Audrey, Ardern-Jones, Chris H, Bangma, Elena, Castro, David, Dearnaley, Diana M, Eccles, Karen, Tricker, Jorunn, Eyfjord, Alison, Falconer, Christopher, Foster, Henrik, Gronberg, Freddie C, Hamdy, Vigdis, Stefansdottir, Vincent, Khoo, Geoffrey J, Lindeman, Jan, Lubinski, Karol, Axcrona, Christos, Mikropoulos, Anita, Mitra, Clare, Moynihan, Gadi, Rennert, Mohnish, Suri, Penny, Wilson, Tim, Dudderidge, Judith, Offman, Zsofia, Kote-Jarai, Andrew, Vickers, Hans, Lilja, Rosalind A, Eeles, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland

Subjects
Adult, Male, Prostate cancer, Gen, Targeted prostate screening, Genetic Carrier Screening, Urology, Genes, BRCA2, Genes, BRCA1, Prostatic Neoplasms, Blöðruhálskirtilskrabbamein, Middle Aged, Prostate-Specific Antigen, BRCA1, BRCA2, Prostate-specific-antigen, Humans, Kallikreins, Prospective Studies, Þvagfærasjúkdómar, Early Detection of Cancer, Germ-Line Mutation, Aged
Abstract

Publisher's version (útgefin grein)., Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. Design, setting, and participants: Men aged 40–69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Patient summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening. © 2019 The Authors We demonstrate that after 3 yr of prostate-specific-antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening., We demonstrate that, after four annual PSA screening rounds, BRCA2 mutation carriers have a higher incidence of PrCa, are diagnosed at a younger age, and present with more clinically significant tumours than BRCA2 noncarriers. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Therefore, these data support the use of systematic PSA screening in male BRCA2 carriers. Author contributions : Rosalind A. Eeles had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design : Aaronson, Ardern-Jones, Bancroft, Bangma, Castro, Dearnaley, Eccles, Evans, Eyfjord, Falconer, Foster, Gronberg, Hamdy, Johannsson, Khoo, Kote-Jarai, Lilja, Lindeman, Lubinski, Mahle, Mikropoulos, Mitra, Moynihan, Page, Rennert, Suri. Acquisition of data: All authors. Analysis and interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis : Page, Bancroft, Brook, Assel, Vickers, Lilja. Obtaining funding : Eeles and all IMPACT collaborating sites obtained their own funding for running the study at their site. Administrative, technical, or material support: All authors. Supervision: Eeles. Other : None. Financial disclosures: Rosalind A. Eeles certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Hans Lilja holds patents for intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The patents have been licensed and commercialised as the 4 Kscore by OPKO Health. Drs. Vickers and Lilja receive royalties from sales of this test. Additionally, Dr. Lilja owns stock and Dr. Vickers owns stock options in OPKO. Professor Rosalind Eeles: Royal Marsden Hospital—Nov 2017; support from Janssen; honorarium as speaker £1100; University of Chicago invited talk May 2018; honorarium as speaker Rosalind A. Eeles certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Hans Lilja holds patents for intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The patents have been licensed and commercialised as the 4 Kscore by OPKO Health. Drs. Vickers and Lilja receive royalties from sales of this test. Additionally, Dr. Lilja owns stock and Dr. Vickers owns stock options in OPKO. Professor Rosalind Eeles: Royal Marsden Hospital—Nov 2017; support from Janssen; honorarium as speaker £1100; University of Chicago invited talk May 2018; honorarium as speaker $1000. The remaining authors have no other conflict of interest to declare.000. The remaining authors have no other conflict of interest to declare. Funding/Support and role of the sponsor : This research is coordinated by the Institute of Cancer Research, London, UK, and is supported by grants from Cancer Research UK (grant references C5047/A21332, C5047/A13232, and C5047/A17528) and the Ronald and Rita McAulay Foundation. Judith Offman is supported by Cancer Research UK Programme Grant reference C8161/A16892. Mr. and Mrs. Jack Baker are acknowledged for supporting the study in NorthShore University HealthSystem, Evanston, IL, USA and Myriad Genetics Laboratory, Salt Lake City, UT, USA, for providing research BRCA testing rates for NorthShore University HealthSystem patients. We acknowledge funding from the National Institute for Health Research (NIHR) to the Biomedical Research Center at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, at Manchester University Foundation Trust (IS-BRC-1215-20007), the Oxford Biomedical Research Centre Program, and the Cambridge Clinical Research Centre, NIHR Cambridge Biomedical Research Centre. We acknowledge that in Australia, this project was cofunded by Cancer Council Tasmania and Cancer Australia (grant number 1006349 [2011–2013]), Prostate Cancer Foundation of Australia (grant number PCFA PRO4 [2008]), Cancer Councils of Victoria and South Australia (grant number 400048 [2006–2008]), the Victorian Cancer Agency Clinical Trial Capacity CTCB08_14, Cancer Australia and Prostate Cancer Foundation of Australia (2014–2016; grant number 1059423), and Translational grants EOI09_50. The Association of International Cancer Research funded data collection in The Netherlands (AICR 10-0596). We acknowledge funding from the Basser Center for BRCA (to Susan Domchek). This work was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748), a SPORE grant in Prostate Cancer to Dr. H. Scher (P50-CA92629), the Sidney Kimmel Center for Prostate and Urologic Cancers, David H. Koch through the Prostate Cancer Foundation. This work was also supported in part by the NIHR Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (CAN 2017/559), the Swedish Research Council (VR-MH project no. 2016-02974), and General Hospital in Malmö Foundation for Combating Cancer. We acknowledge funding from the Slovenian Research Agency, Research programme P3-0352. We thank CERCA Program/Generalitat de Catalunya for their institutional support. Elena Castro acknowledges funding from Prostate Cancer Foundation. We acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad), “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI16/00563, JR18/00011 and CIBERONC), and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). We acknowledge funding support from Fundação para a Ciência e a Tecnologia to the IPO Porto study (project grant PTDC/DTP-PIC/1308/2014 to Manuel R. Teixeira and fellowship grant SFRH/BD/116557/2016 to Marta Cardoso).

Published
2019

9. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author

Jose Chacon, Katja Ziegler-Löhr, Kamran Rashid, Stanley Madretsma, Hortense Laharie Mineur, Soo Hyeon Lee, Bohuslav Melichar, Jasna Pesic, Julia Hall, Jörg Schilling, Paola Morales Espinosa, Wendy Taylor, Francesco Cognetti, Doris Augustin, Ines Sandri, Laura Murillo Jaso, Alejandro Juarez Ramiro, Nora Artagaveytia, Rocio Reategui, Nataliia Voitko, Teresa Gamucci, Lisa H Barraclough, Jérôme Alexandre, Mohammed Butt, Frank Priou, A.J. van de Wouw, Cristina Marinela Oprean, Isabel Alonso, Suzana Vasovic, Fernando Roque, Marc Thill, Viktoria Dvornichenko, K. Bouzid, Idris Yucel, Andrea Stefek, Jose Manuel Lopez Vega, Daniil Stroyakovskiy, R. Chiara Forcignanò, Mohammed Harb, Andrzej Mruk, Jana Prausová, Lydia Dreosti, Prabir Chakraborti, Armando Santoro, Lee Wei Ching, Anna Tuczek, Jane Beith, Larisa Ciule, Hakan Bozcuk, Antonino Musolino, Hartmut Kristeleit, Clare Crowley, T.C. Kok, Dhurata Koroveshi, Natasha Mithal, Laura Garcia Sanchis, Stephan Henschen, Carmen Cañabate Arias, A. Contu, Antoaneta Tomova, Alper Sevinc, Helga Droogendijk, Gustavo Fernando Ismael, Konstantinos Papazisis, Laurent Gasnault, Sandra Bakker, Judit Kocsis, Bernd Christensen, Stephen Kelly, Rosana Jarcau, Christian Jackisch, George Fountzilas, Cyril Foa, Annebeth W. Haringhuizen, Silvia Neciosup, Juan Matos Santos, Finlander Rosales Osegueda, Robinson Rodriguez, Marcus Schmidt, Bart de Valk, Kathryn Wright, A.S. Dhadda, Elizabeth Sherwin, Sabino De Placido, Luigi Cavanna, Joelle Egreteau, Shazza Rehman, Giacomo Allegrini, Doerte Luedders, Poovandren Govender, Hugues Barletta, Iztok Takač, Yuraima Garcia, Michael Green, Geneviève Jolimoy, Marcela Urrego, Chanyoot Bandidwattanawong, Vito Lorusso, Annette van der Velden, Rene Muñoz, Djumhana Atmakusuma, Christos Papandreou, Craig Macmillan, Hassan Errihani, Iris Schrader, Isabelle Desmoulins, Jean-Marc Ferrero, Mohamed Idris, B. Ataseven, Andre Farrokh, Isabelle Moullet, Iain R. Macpherson, N. Al-Sakaff, Stephen Chia, Blanca Hernando Fernandez De Aranguiz, Lorena Lion, Alexandros Ardavanis, Ani Zlatareva-Petrova, Ernesto Pablo Korbenfeld, Hugo Castro, Mirta Garcia, Heike Passmann-Kegel, Lionel Uwer, Gary Richardson, Marion Paul, Georgia Demetriou, Andreas Köhler, V. Kovcin, Eliot Sims, Gerasimos Aravantinos, Adriana Dominguez, Daniel Rauch, Greta Beyer, Laurence J. C. van Warmerdam, Roberto Bordonaro, Raymond Ng, David Coeffic, Rostislav Vyzula, Bernard Leduc, Jozef Mardiak, Andrea Pigi, Ingo Runnebaum, Jose Angel Garcia Saenz, Areewan Somwangprasert, Cristina Llorca Ferrandiz, Coskun Hasan Senol, Martin Griesshammer, Friedrich Overkamp, Suzanne Nguyen, Maria Turdean, Udaiveer Panwar, Zsuzsanna Nagy, Francesco Giotta, Andreas Schneeweiss, Teresa Ramon y Cajal Asensio, Jae Hong Seo, Joohyuk Sohn, Jean-Philippe Jacquin, Daniela Grecea, Jasmina Nedovic, Arrate Plazaola Alcibar, Tadeusz Pienkowski, Jetske M. Meerum Terwogt, Elmar Stickeler, Hazem I. Assi, Vadim Shirinkin, Grzegorz Slomian, Etela Mišurová, Roberto Hegg, K. Friedrichs, Corinne Dagada, Jean-François Berdah, Fulden Yumuk, Alexandru Eniu, Amit Chakrabarti, Mathias Fehr, Christoph Salat, Dan Lungulescu, Heinrik Martin Strebel, Antonio Llombart Cussac, Rémy Largillier, Stefan Curescu, Albert von der Assen, Emmanuel Guardiola, Andras Csejtei, Tamas Hickish, Krzysztof Krzemieniecki, Yaroslav Shparyk, Ramon Perez Carrion, Michela Donadio, Purificacion Martinez del Prado, Sandra Franco, J.J. Braun, Michael Friedlander, Suhail Anwar, Thierry Petit, Sarah Smith, Rafael Gutierrez Pilarte, Laia Garrigos Cubells, Frans L. G. Erdkamp, Jedzada Maneechavakajorn, Mastura Yusof, Jocelyn Adams, Diana Cascallar, Luis Antonio Fernandez Morales, Max S. Mano, Simon Waters, Carlos Beato, Philippe Martin, Martin Hogg, Isabelle Sillet Bach, Monica Casalnuovo, Klara Mezei, Alexey Manikhas, Margarida Damasceno, Sergey Emelyanov, Gabriella Mariani, Kecman Gordana, Gianfilippo Bertelli, Ignacio Pelaez Fernandez, Damir Vrbanec, Maria Wagnerova, Johannes Petrus Jordaan, Marina Cazzaniga, Mustafa Deryal, Ruth Davis, Abdurrahman Isikdogan, Sanjay Raj, José Juan Illarramendi Mañas, Vinod Ganju, Maria Dolores Torregrosa Maicas, Glenda Ramos, Nugroho Prayogo, H. Orfeuvre, Filipovic S, Joke Tio, Andrew Redfern, M. Shing, Eduardo Yanez, Khalil Zaman, Jin-Seok Ahn, Dino Amadori, Bahriye Aktas, Miriam O'Connor, Uta Ringsdorf, Christophe Desauw, J. Gligorov, Jorge Corona, Michele De Laurentiis, Arthur Wischnik, Paolo Pedrazzoli, Katalin Boér, Caroline Archer, Anne Kendall, Ori Freedman, Maya Tsakova, Dana Lucia Stanculeanu, Kevin Patterson, Cathy Kelly, Nellie Lay Chin Cheah, X. Artignan, Anil A. Joy, Steffi Busch, Monica Nave, Bryan Hennessy, Lorenzo Livi, X. Pivot, R.J.B. Blaisse, Adolfo Murias Rosales, Juan Carlos Alcedo, Dalila Marcano, Emmanuel Beguier, Andreas Müller, László Csaba Mangel, Christina Schlatter, Fernando Gaion, Tjoung-Won Park-Simon, Sebastian Wojcinski, Ute Bückner, Florinel Badulescu, Cynthia Mayte Villarreal Garza, Rozenn Allerton, Mikhail Lichinitser, Damir Gugić, Manuela Rabaglio, Jens Kisro, Iris Scheffen, Vincent Phua, Marc A. Bollet, Giampaolo Biti, M. Verrill, Adrien Melis, Andrew M Wardley, Ali Arican, Hamdy A. Azim, Lelia-Eveline Bauer, Tsai-Wang Chang, Nik Hauser, René Lazaro González Mendoza, Dominique Jaubert, Samreen Ahmed, Mazhar Shah, János Szántó, Kunibert Latos, Xavier Pivot, Helen Gogas, Elona Juozaityte, Luca Moscetti, Helene Simon, Giacomo Carterni, Dan-Corneliu Jinga, Olivia Pagani, Elena Rota Caremoli, Esther Arbona, Cornelia Liedtke, Stylianos Kakolyris, Abdulla Alhasso, Omalkhair Abulkhair, Jose Ponce Lorenzo, Julian Singer, Tony Branson, Claudia Hänle, Ingvild Mjaaland, Chiun-Sheng Huang, Heri Fadjari, Jonathan Joffe, Laetitia Stefani, Dieter Lampe, Franck Burki, S. Lauer, Sabine Schmatloch, Gracieux Fernando, Dina Sakaeva, Christina Balser, Michael Martin, Nora Bittner, Andrea Heider, Antonio Frassoldati, Serafin Morales Murillo, Hakan Akbulut, Saad Tahir, Tilmann Lantzsch, Christine Brezden-Masley, Vanessa Helena, Tran Van Thuan, F.E. de Jongh, Roger K.C. Ngan, Elke Faust, Hugues Bourgeois, Flora Li Tze Chong, Nehal Masood, Keun Seok Lee, J. Bishop, Mathias Warm, Dimitris Mavroudis, Petrosian Veersamy, Judith Fraser, Andres Garcia-Palomo Perez, Heiko Graf, Vanesa Quiroga Garcia, Jyh-Cherng Yu, Maria Jose Villanueva Silva, Elke Simon, Diana Aleman, Kazim Uygun, Cosima Brucker, Michael Weigel, Volkmar Müller, Djohan Kurnianda, Duncan Wheatley, Amr Abdel Aziz, Benno Lex, Laura G. Estévez, Darren Teoh, María Isabel León, Noemia Afonso, Frances Yuille, Amelia Tienghi, Gernot Seipelt, Jose Alberto Nogueira, Dumitru Filip, Zafar Malik, Fatima Cardoso, Giorgio Cruciani, Winnie Yeo, Luis Vera, Santiago Gonzalez Santiago, Richard North, M.W. Dercksen, Zsolt Horváth, Noelia Martinez Jañez, Marta Mion, Marcela Ferrari, Natalia Valdiviezo, Oana Zveltlana Cojocarasu, Alessandra Morelle, Medy Tsalic, Sonia Pernas Simon, Christoph Maintz, Daniele Farci, Alvaro Edson Lessa, Jeremy Monge, Joseph Gligorov, Anthony Neal, Norberto Batista Lopez, Piotr Tomczak, Yesim Eralp, Kasan Seetalarom, Thitiya (Sirisinha) Dejthevaporn, Jamal Zekri, Steven John Proctor, Saira Nasim, Muireann Kelleher, Eftal Yucel, Quirine Clementine van Rossum-Schornagel, Linda Coate, Paolo Marchetti, Theresa Howe, Carlos Alberto Hernandez, Roberto Torres, Konstanta Timcheva, Evaristo Maiello, Anita Prechtl, Jamil Asselah, Branislav Bystricky, Kate Scatchard, Zeba Aziz, Jaroslava Leskova, Sherko Kuemmel, Paolo Bidoli, Richard Ashford, Piotr Sawrycki, Claude Bressac, Alberto Bottini, Pilar Lopez Alvarez, Nadine Dohollou, Alejandro Andres Acevedo Gaete, M. De Laurentiis, T.J. Smilde, Andrew Proctor, Catherine Prady, Michele Aieta, Jan Henry Svensson, Reda Garidi, Erik Wist, Antonia Perello Martorell, Mohammed Jaloudi, Graeme Lumsden, Eva-Maria Grischke, Ali Youssef, Annemieke van der Padt, Kadri Altundag, Christina Bechtner, Mireille Mousseau, Heba El Zawahry, Maartje Los, Alvydas Česas, Alfredo Falcone, Salima Hamizi, Franchette W P J van den Berkmortel, Cesar Estuardo Hernandez-Monroy, K.H. Jung, Swati Kulkarni, R.K. Agrawal, Hwei Chung Wang, Hany Eldeeb, Fredrika Killander, Jose Luis Alonso Romero, Antonio Pazzola, Daan ten Bokkel Huinink, Mario Campone, Beena C.R. Devi, Florence Dalenc, Pedro Jimenez Gallego, Mawin Vongsaisuwon, Timur Ceric, Chantal Bernard Marty, R. A. Popescu, J. van den Bosch, Luis Matamala, Sylvia Ruth, Maria Litwiniuk, Maria Lomas Garrido, Mark Churn, Christian Kersten, Francesco Del Piano, Eddie Herman Tanggo, Antonio Fernandez Aramburo, Kyung Hae Jung, Christos Papadimitriou, Hamdy Abdel Azeem, Patricia Bastick, Tobias Hesse, Maree Colosimo, Lucia Gonzalez Cortijo, Mark Verrill, Gligorov, J, Ataseven, B, Verrill, M, De Laurentiis, M, Jung, K. H, Azim, H. A, Al-sakaff, N, Lauer, S, Shing, M, Pivot, X., de Laurentiis, M, Jung, K, Azim, H, Al-Sakaff, N, Pivot, X, Koroveshi, D, Bouzid, K, Casalnuovo, M, Cascallar, D, Korbenfeld, E, Bastick, P, Beith, J, Colosimo, M, Friedlander, M, Ganju, V, Green, M, Patterson, K, Redfern, A, Richardson, G, Ceric, T, Gordana, K, Beato, C, Ferrari, M, Hegg, R, Helena, V, Ismael, G, Lessa, A, Mano, M, Morelle, A, Nogueira, J, Timcheva, K, Tomova, A, Tsakova, M, Zlatareva-Petrova, A, Asselah, J, Assi, H, Brezden-Masley, C, Chia, S, Freedman, O, Harb, M, Joy, A, Kulkarni, S, Prady, C, Gaete, A, Matamala, L, Torres, R, Yanez, E, Franco, S, Urrego, M, Gugic, D, Vrbanec, D, Melichar, B, Prausova, J, Vyzula, R, Pilarte, R, Leon, M, Munoz, R, Ramos, G, Azeem, H, Aziz, A, El Zawahry, H, Osegueda, F, Alexandre, J, Artignan, X, Barletta, H, Beguier, E, Berdah, J, Marty, C, Bollet, M, Bourgeois, H, Bressac, C, Burki, F, Campone, M, Coeffic, D, Cojocarasu, O, Dagada, C, Dalenc, F, Del Piano, F, Desauw, C, Desmoulins, I, Dohollou, N, Egreteau, J, Ferrero, J, Foa, C, Garidi, R, Gasnault, L, Guardiola, E, Hamizi, S, Jarcau, R, Jacquin, J, Jaubert, D, Jolimoy, G, Mineur, H, Largillier, R, Leduc, B, Martin, P, Melis, A, Monge, J, Moullet, I, Mousseau, M, Nguyen, S, Orfeuvre, H, Petit, T, Priou, F, Bach, I, Simon, H, Stefani, L, Uwer, L, Youssef, A, Aktas, B, von der Assen, A, Augustin, D, Balser, C, Bauer, L, Bechtner, C, Beyer, G, Brucker, C, Buckner, U, Busch, S, Christensen, B, Deryal, M, Farrokh, A, Faust, E, Friedrichs, K, Graf, H, Griesshammer, M, Grischke, E, Hanle, C, Heider, A, Henschen, S, Hesse, T, Jackisch, C, Kisro, J, Kohler, A, Kuemmel, S, Lampe, D, Lantzsch, T, Latos, K, Lex, B, Liedtke, C, Luedders, D, Maintz, C, Muller, V, Overkamp, F, Park-Simon, T, Paul, M, Prechtl, A, Ringsdorf, U, Runnebaum, I, Ruth, S, Salat, C, Scheffen, I, Schilling, J, Schmatloch, S, Schmidt, M, Schneeweiss, A, Schrader, I, Seipelt, G, Simon, E, Stefek, A, Stickeler, E, Thill, M, Tio, J, Tuczek, A, Warm, M, Weigel, M, Wischnik, A, Wojcinski, S, Ziegler-Lohr, K, Aravantinos, G, Ardavanis, A, Fountzilas, G, Gogas, H, Kakolyris, S, Mavroudis, D, Papadimitriou, C, Papandreou, C, Papazisis, K, Castro, H, Hernandez-Monroy, C, Ngan, R, Yeo, W, Bittner, N, Boer, K, Csejtei, A, Horvath, Z, Kocsis, J, Mangel, L, Mezei, K, Nagy, Z, Szanto, J, Atmakusuma, D, Fadjari, H, Kurnianda, D, Prayogo, N, Tanggo, E, Coate, L, Hennessy, B, Kelly, C, Martin, M, Nasim, S, O'Connor, M, Aieta, M, Allegrini, G, Amadori, D, Bidoli, P, Biti, G, Bordonaro, R, Bottini, A, Carterni, G, Cavanna, L, Cazzaniga, M, Cognetti, F, Contu, A, Cruciani, G, Donadio, M, Falcone, A, Farci, D, Forcignano, R, Frassoldati, A, Gaion, F, Gamucci, T, Giotta, F, Livi, L, Lorusso, V, Maiello, E, Marchetti, P, Mariani, G, Mion, M, Moscetti, L, Musolino, A, Pazzola, A, Pedrazzoli, P, Pigi, A, de Placido, S, Caremoli, E, Santoro, A, Tienghi, A, Ahn, J, Lee, K, Lee, S, Seo, J, Sohn, J, Cesas, A, Juozaityte, E, Cheah, N, Chong, F, Devi, B, Phua, V, Teoh, D, Ching, L, Yusof, M, Corona, J, Dominguez, A, Mendoza, R, Hernandez, C, Ramiro, A, Santos, J, Espinosa, P, Villarreal Garza, C, Errihani, H, Bakker, S, van den Berkmortel, F, Blaisse, R, Huinink, D, van den Bosch, J, Braun, J, Dercksen, M, Droogendijk, H, Erdkamp, F, Haringhuizen, A, de Jongh, F, Kok, T, Los, M, Madretsma, S, Terwogt, J, van der Padt, A, van Rossum-Schornagel, Q, Smilde, T, de Valk, B, van der Velden, A, van Warmerdam, L, van de Wouw, A, North, R, Kersten, C, Mjaaland, I, Wist, E, Aziz, Z, Masood, N, Rashid, K, Shah, M, Alcedo, J, Aleman, D, Neciosup, S, Reategui, R, Valdiviezo, N, Vera, L, Fernando, G, Roque, F, Strebel, H, Krzemieniecki, K, Litwiniuk, M, Mruk, A, Pienkowski, T, Sawrycki, P, Slomian, G, Tomczak, P, Afonso, N, Cardoso, F, Damasceno, M, Nave, M, Badulescu, F, Ciule, L, Curescu, S, Eniu, A, Filip, D, Grecea, D, Jinga, D, Lungulescu, D, Oprean, C, Stanculeanu, D, Turdean, M, Dvornichenko, V, Emelyanov, S, Lichinitser, M, Manikhas, A, Sakaeva, D, Shirinkin, V, Stroyakovskiy, D, Abulkhair, O, Zekri, J, Filipovic, S, Kovcin, V, Nedovic, J, Pesic, J, Vasovic, S, Ng, R, Bystricky, B, Leskova, J, Mardiak, J, Misurova, E, Wagnerova, M, Takac, I, Demetriou, G, Dreosti, L, Govender, P, Jordaan, J, Veersamy, P, Romero, J, Lopez, N, Arias, C, Chacon, J, Aramburo, A, Morales, L, Garcia, M, Estevez, L, Garcia-Palomo Perez, A, Garcia Saenz, J, Garcia Sanchis, L, Cubells, L, Cortijo, L, Santiago, S, De Aranguiz, B, Manas, J, Gallego, P, Cussac, A, Ferrandiz, C, Garrido, M, Alvarez, P, Vega, J, Del Prado, P, Janez, N, Murillo, S, Rosales, A, Jaso, L, Fernandez, I, Martorell, A, Carrion, R, Simon, S, Alcibar, A, Lorenzo, J, Garcia, V, Asensio, T, Maicas, M, Villanueva Silva, M, Killander, F, Svensson, J, Fehr, M, Hauser, N, Muller, A, Pagani, O, Passmann-Kegel, H, Popescu, R, Rabaglio, M, Rauch, D, Schlatter, C, Zaman, K, Chang, T, Huang, C, Wang, H, Yu, J, Bandidwattanawong, C, Maneechavakajorn, J, Seetalarom, K, Dejthevaporn, T, Somwangprasert, A, Vongsaisuwon, M, Akbulut, H, Altundag, K, Arican, A, Bozcuk, H, Eralp, Y, Idris, M, Isikdogan, A, Senol, C, Sevinc, A, Uygun, K, Yucel, E, Yucel, I, Yumuk, F, Shparyk, Y, Voitko, N, Jaloudi, M, Adams, J, Agrawal, R, Ahmed, S, Alhasso, A, Allerton, R, Anwar, S, Archer, C, Ashford, R, Barraclough, L, Bertelli, G, Bishop, J, Branson, T, Butt, M, Chakrabarti, A, Chakraborti, P, Churn, M, Crowley, C, Davis, R, Dhadda, A, Eldeeb, H, Fraser, J, Hall, J, Hickish, T, Hogg, M, Howe, T, Joffe, J, Kelleher, M, Kelly, S, Kendall, A, Kristeleit, H, Lumsden, G, Macmillan, C, Macpherson, I, Malik, Z, Mithal, N, Neal, A, Panwar, U, Proctor, A, Proctor, S, Raj, S, Rehman, S, Sandri, I, Scatchard, K, Sherwin, E, Sims, E, Singer, J, Smith, S, Tahir, S, Taylor, W, Tsalic, M, Wardley, A, Waters, S, Wheatley, D, Wright, K, Yuille, F, Alonso, I, Artagaveytia, N, Rodriguez, R, Arbona, E, Garcia, Y, Lion, L, Marcano, D, and Van Thuan, T

Subjects
0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, Medizin, Antineoplastic Agent, 0302 clinical medicine, Breast cancer, Trastuzumab, Adjuvant, Aged, 80 and over, education.field_of_study, Middle Aged, HER2/neu, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Herceptin, Subcutaneous, subcutaneous, Female, Survival Analysi, Breast Neoplasm, medicine.drug, Human, Adult, medicine.medical_specialty, Injections, Subcutaneous, Population, Socio-culturale, Antineoplastic Agents, Breast Neoplasms, Injections, Subcutaneou, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Adjuvant therapy, Humans, Subcutaneou, education, Adverse effect, Aged, Chemotherapy, Adjuvant, breast cancer, HER2/neu, herceptin, trastuzumab, business.industry, medicine.disease, Survival Analysis, Surgery, Discontinuation, 030104 developmental biology, business
Abstract

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Published
2017

10. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Author

Gligorov, J., primary, Ataseven, B., additional, Verrill, M., additional, De Laurentiis, M., additional, Jung, K.H., additional, Azim, H.A., additional, Al-Sakaff, N., additional, Lauer, S., additional, Shing, M., additional, Pivot, X., additional, Koroveshi, Dhurata, additional, Bouzid, Kamel, additional, Casalnuovo, Monica, additional, Cascallar, Diana, additional, Korbenfeld, Ernesto Pablo, additional, Bastick, Patricia, additional, Beith, Jane, additional, Colosimo, Maree, additional, Friedlander, Michael, additional, Ganju, Vinod, additional, Green, Michael, additional, Patterson, Kevin, additional, Redfern, Andrew, additional, Richardson, Gary, additional, Ceric, Timur, additional, Gordana, Kecman, additional, Beato, Carlos Augusto, additional, Ferrari, Marcela, additional, Hegg, Roberto, additional, Helena, Vanessa, additional, Ismael, Gustavo Fernando, additional, Lessa, Alvaro Edson, additional, Mano, Max, additional, Morelle, Alessandra, additional, Nogueira, Jose Alberto, additional, Timcheva, Konstanta, additional, Tomova, Antoaneta, additional, Tsakova, Maya, additional, Zlatareva-Petrova, Ani, additional, Asselah, Jamil, additional, Assi, Hazem, additional, Brezden-Masley, Christine, additional, Chia, Stephen, additional, Freedman, Ori, additional, Harb, Mohammed, additional, Joy, Anil Abraham, additional, Kulkarni, Swati, additional, Prady, Catherine, additional, Gaete, Alejandro Andres Acevedo, additional, Matamala, Luis, additional, Torres, Roberto, additional, Yanez, Eduardo, additional, Franco, Sandra, additional, Urrego, Marcela, additional, Gugić, Damir, additional, Vrbanec, Damir, additional, Melichar, Bohuslav, additional, Prausová, Jana, additional, Vyzula, Rostislav, additional, Pilarte, Rafael Gutierrez, additional, León, María Isabel, additional, Muñoz, Rene, additional, Ramos, Glenda, additional, Azeem, Hamdy Abdel, additional, Aziz, Amr Abdel, additional, El Zawahry, Heba, additional, Osegueda, Finlander Rosales, additional, Alexandre, Jerome, additional, Artignan, Xavier, additional, Barletta, Hugues, additional, Beguier, Emmanuel, additional, Berdah, Jean-François, additional, Marty, Chantal Bernard, additional, Bollet, Marc, additional, Bourgeois, Hugues, additional, Bressac, Claude, additional, Burki, Franck, additional, Campone, Mario, additional, Coeffic, David, additional, Cojocarasu, Oana Zveltlana, additional, Dagada, Corinne, additional, Dalenc, Florence, additional, Del Piano, Francesco, additional, Desauw, Christophe, additional, Desmoulins, Isabelle, additional, Dohollou, Nadine, additional, Egreteau, Joelle, additional, Ferrero, Jean-Marc, additional, Foa, Cyril, additional, Garidi, Reda, additional, Gasnault, Laurent, additional, Gligorov, Joseph, additional, Guardiola, Emmanuel, additional, Hamizi, Salima, additional, Jarcau, Rosana, additional, Jacquin, Jean-Philippe, additional, Jaubert, Dominique, additional, Jolimoy, Geneviève, additional, Mineur, Hortense Laharie, additional, Largillier, Remy, additional, Leduc, Bernard, additional, Martin, Philippe, additional, Melis, Adrien, additional, Monge, Jeremy, additional, Moullet, Isabelle, additional, Mousseau, Mireille, additional, Nguyen, Suzanne, additional, Orfeuvre, Hubert, additional, Petit, Thierry, additional, Pivot, Xavier, additional, Priou, Frank, additional, Bach, Isabelle Sillet, additional, Simon, Helene, additional, Stefani, Laetitia, additional, Uwer, Lionel, additional, Youssef, Ali, additional, Aktas, Bahriye, additional, von der Assen, Albert, additional, Augustin, Doris, additional, Balser, Christina, additional, Bauer, Lelia-Eveline, additional, Bechtner, Christina, additional, Beyer, Greta, additional, Brucker, Cosima, additional, Bückner, Ute, additional, Busch, Steffi, additional, Christensen, Bernd, additional, Deryal, Mustafa, additional, Farrokh, Andre, additional, Faust, Elke, additional, Friedrichs, Kay, additional, Graf, Heiko, additional, Griesshammer, Martin, additional, Grischke, Eva-Maria, additional, Hänle, Claudia, additional, Heider, Andrea, additional, Henschen, Stephan, additional, Hesse, Tobias, additional, Jackisch, Christian, additional, Kisro, Jens, additional, Köhler, Andreas, additional, Kuemmel, Sherko, additional, Lampe, Dieter, additional, Lantzsch, Tilmann, additional, Latos, Kunibert, additional, Lex, Benno, additional, Liedtke, Cornelia, additional, Luedders, Doerte, additional, Maintz, Christoph, additional, Müller, Volkmar, additional, Overkamp, Friedrich, additional, Park-Simon, Tjoung-won, additional, Paul, Marion, additional, Prechtl, Anita, additional, Ringsdorf, Uta, additional, Runnebaum, Ingo, additional, Ruth, Sylvia, additional, Salat, Christoph, additional, Scheffen, Iris, additional, Schilling, Jörg, additional, Schmatloch, Sabine, additional, Schmidt, Marcus, additional, Schneeweiss, Andreas, additional, Schrader, Iris, additional, Seipelt, Gernot, additional, Simon, Elke, additional, Stefek, Andrea, additional, Stickeler, Elmar, additional, Thill, Marc, additional, Tio, Joke, additional, Tuczek, Anna, additional, Warm, Mathias, additional, Weigel, Michael, additional, Wischnik, Arthur, additional, Wojcinski, Sebastian, additional, Ziegler-Löhr, Katja, additional, Aravantinos, Gerasimos, additional, Ardavanis, Alexandros, additional, Fountzilas, George, additional, Gogas, Helen, additional, Kakolyris, Stylianos, additional, Mavroudis, Dimitris, additional, Papadimitriou, Christos, additional, Papandreou, Christos, additional, Papazisis, Konstantinos, additional, Castro, Hugo, additional, Hernandez-Monroy, Cesar Estuardo, additional, Ngan, Roger, additional, Yeo, Winnie, additional, Bittner, Nora, additional, Boer, Katalin, additional, Csejtei, Andras, additional, Horvath, Zsolt, additional, Kocsis, Judit, additional, Mangel, László Csaba, additional, Mezei, Klara, additional, Nagy, Zsuzsanna, additional, Szanto, Janos, additional, Atmakusuma, Djumhana, additional, Fadjari, Heri, additional, Kurnianda, Djohan, additional, Prayogo, Nugroho, additional, Tanggo, Eddie Herman, additional, Coate, Linda, additional, Hennessy, Bryan, additional, Kelly, Cathy, additional, Martin, Michael, additional, Nasim, Saira, additional, O'Connor, Miriam, additional, Aieta, Michele, additional, Allegrini, Giacomo, additional, Amadori, Dino, additional, Bidoli, Paolo, additional, Biti, Giampaolo, additional, Bordonaro, Roberto, additional, Bottini, Alberto, additional, Carterni, Giacomo, additional, Cavanna, Luigi, additional, Cazzaniga, Marina, additional, Cognetti, Francesco, additional, Contu, Antonio, additional, Cruciani, Giorgio, additional, Donadio, Michela, additional, Falcone, Alfredo, additional, Farci, Daniele, additional, Forcignanò, R. Chiara, additional, Frassoldati, Antonio, additional, Gaion, Fernando, additional, Gamucci, Teresa, additional, Giotta, Francesco, additional, de Laurentiis, Michele, additional, Livi, Lorenzo, additional, Lorusso, Vito, additional, Maiello, Evaristo, additional, Marchetti, Paolo, additional, Mariani, Gabriella, additional, Mion, Marta, additional, Moscetti, Luca, additional, Musolino, Antonino, additional, Pazzola, Antonio, additional, Pedrazzoli, Paolo, additional, Pigi, Andrea, additional, de Placido, Sabino, additional, Caremoli, Elena Rota, additional, Santoro, Armando, additional, Tienghi, Amelia, additional, Ahn, Jin-Seok, additional, Jung, Kyung Hae, additional, Lee, Keun Seok, additional, Lee, Soo Hyeon, additional, Seo, Jae Hong, additional, Sohn, Joo-Hyuk, additional, Cesas, Alvydas, additional, Juozaityte, Elona, additional, Cheah, Nellie Lay Chin, additional, Chong, Flora Li Tze, additional, Devi, Beena C.R., additional, Phua, Vincent, additional, Teoh, Darren, additional, Ching, Lee Wei, additional, Yusof, Mastura, additional, Corona, Jorge, additional, Dominguez, Adriana, additional, Mendoza, René Lazaro González, additional, Hernandez, Carlos Alberto, additional, Ramiro, Alejandro Juarez, additional, Santos, Juan Matos, additional, Espinosa, Paola Morales, additional, Villarreal Garza, Cynthia Mayte, additional, Errihani, Hassan, additional, Bakker, Sandra, additional, van den Berkmortel, Franchette, additional, Blaisse, R.J.B., additional, Huinink, Daan ten Bokkel, additional, van den Bosch, J., additional, Braun, J.J., additional, Dercksen, M.W., additional, Droogendijk, Helga, additional, Erdkamp, Frans, additional, Haringhuizen, Annebeth, additional, de Jongh, F.E., additional, Kok, T.C., additional, Los, Maartje, additional, Madretsma, Stanley, additional, Terwogt, Jetske M. Meerum, additional, van der Padt, Annemieke, additional, van Rossum-Schornagel, Quirine Clementine, additional, Smilde, T.J., additional, de Valk, Bart, additional, van der Velden, Annette, additional, van Warmerdam, Laurence, additional, van de Wouw, A.J., additional, North, Richard, additional, Kersten, Christian, additional, Mjaaland, Ingvild, additional, Wist, Erik, additional, Aziz, Zeba, additional, Masood, Nehal, additional, Rashid, Kamran, additional, Shah, Mazhar, additional, Alcedo, Juan Carlos, additional, Aleman, Diana, additional, Neciosup, Silvia, additional, Reategui, Rocio, additional, Valdiviezo, Natalia, additional, Vera, Luis, additional, Fernando, Gracieux, additional, Roque, Fernando, additional, Strebel, Heinrik Martin, additional, Krzemieniecki, Krzysztof, additional, Litwiniuk, Maria, additional, Mruk, Andrzej, additional, Pienkowski, Tadeusz, additional, Sawrycki, Piotr, additional, Slomian, Grzegorz, additional, Tomczak, Piotr, additional, Afonso, Noemia, additional, Cardoso, Fátima, additional, Damasceno, Margarida, additional, Nave, Monica, additional, Badulescu, Florinel, additional, Ciule, Larisa, additional, Curescu, Stefan, additional, Eniu, Alexandru, additional, Filip, Dumitru, additional, Grecea, Daniela, additional, Jinga, Dan-Corneliu, additional, Lungulescu, Dan, additional, Oprean, Cristina Marinela, additional, Stanculeanu, Dana Lucia, additional, Turdean, Maria, additional, Dvornichenko, Viktoria, additional, Emelyanov, Sergey, additional, Lichinitser, Mikhail, additional, Manikhas, Alexey, additional, Sakaeva, Dina, additional, Shirinkin, Vadim, additional, Stroyakovskiy, Daniil, additional, Abulkhair, Omalkhair, additional, Zekri, Jamal, additional, Filipovic, Sladjana, additional, Kovcin, Vladimir, additional, Nedovic, Jasmina, additional, Pesic, Jasna, additional, Vasovic, Suzana, additional, Ng, Raymond, additional, Bystricky, Branislav, additional, Leskova, Jaroslava, additional, Mardiak, Jozef, additional, Mišurová, Etela, additional, Wagnerova, Maria, additional, Takač, Iztok, additional, Demetriou, Georgia Savva, additional, Dreosti, Lydia, additional, Govender, Poovandren, additional, Jordaan, Johannes Petrus, additional, Veersamy, Petrosian, additional, Romero, Jose Luis Alonso, additional, Lopez, Norberto Batista, additional, Arias, Carmen Cañabate, additional, Chacon, Jose, additional, Aramburo, Antonio Fernandez, additional, Morales, Luis Antonio Fernandez, additional, Garcia, Mirta, additional, Estevez, Laura Garcia, additional, Garcia-Palomo Perez, Andres, additional, Garcia Saenz, Jose Angel, additional, Garcia Sanchis, Laura, additional, Cubells, Laia Garrigos, additional, Cortijo, Lucia Gonzalez, additional, Santiago, Santiago Gonzalez, additional, De Aranguiz, Blanca Hernando Fernandez, additional, Mañas, José Juan Illarramendi, additional, Gallego, Pedro Jimenez, additional, Cussac, Antonio Llombart, additional, Ferrandiz, Cristina Llorca, additional, Garrido, Maria Lomas, additional, Alvarez, Pilar Lopez, additional, Vega, Jose Manuel Lopez, additional, Del Prado, Purificacion Martinez, additional, Jañez, Noelia Martinez, additional, Murillo, Serafin Morales, additional, Rosales, Adolfo Murias, additional, Jaso, Laura Murillo, additional, Fernandez, Ignacio Pelaez, additional, Martorell, Antonia Perello, additional, Carrion, Ramon Perez, additional, Simon, Sonia Pernas, additional, Alcibar, Arrate Plazaola, additional, Lorenzo, Jose Ponce, additional, Garcia, Vanesa Quiroga, additional, Asensio, Teresa Ramon y Cajal, additional, Maicas, Maria Dolores Torregrosa, additional, Villanueva Silva, Maria Jose, additional, Killander, Fredrika, additional, Svensson, Jan Henry, additional, Fehr, Mathias, additional, Hauser, Nik, additional, Müller, Andreas, additional, Pagani, Olivia, additional, Passmann-Kegel, Heike, additional, Popescu, Razvan, additional, Rabaglio, Manuela, additional, Rauch, Daniel, additional, Schlatter, Christina, additional, Zaman, Khalil, additional, Chang, Tsai-Wang, additional, Huang, Chiun-Sheng, additional, Wang, Hwei-Chung, additional, Yu, Jyh-Cherng, additional, Bandidwattanawong, Chanyoot, additional, Maneechavakajorn, Jedzada, additional, Seetalarom, Kasan, additional, Dejthevaporn, Thitiya (Sirisinha), additional, Somwangprasert, Areewan, additional, Vongsaisuwon, Mawin, additional, Akbulut, Hakan, additional, Altundag, Kadri, additional, Arican, Ali, additional, Bozcuk, Hakan, additional, Eralp, Yesim, additional, Idris, Mohamed, additional, Isikdogan, Abdurrahman, additional, Senol, Coskun Hasan, additional, Sevinc, Alper, additional, Uygun, Kazim, additional, Yucel, Eftal, additional, Yucel, Idris, additional, Yumuk, Fulden, additional, Shparyk, Yaroslav, additional, Voitko, Nataliia, additional, Jaloudi, Mohammed, additional, Adams, Jocelyn, additional, Agrawal, Rajiv, additional, Ahmed, Samreen, additional, Alhasso, Abdulla, additional, Allerton, Rozenn, additional, Anwar, Suhail, additional, Archer, Caroline, additional, Ashford, Richard, additional, Barraclough, Lisa, additional, Bertelli, Gianfilippo, additional, Bishop, Jill, additional, Branson, Tony, additional, Butt, Mohammed, additional, Chakrabarti, Amit, additional, Chakraborti, Prabir, additional, Churn, Mark, additional, Crowley, Clare, additional, Davis, Ruth, additional, Dhadda, Amandeep, additional, Eldeeb, Hany, additional, Fraser, Judith, additional, Hall, Julia, additional, Hickish, Tamas, additional, Hogg, Martin, additional, Howe, Theresa, additional, Joffe, Jonathan, additional, Kelleher, Muireann, additional, Kelly, Stephen, additional, Kendall, Anne, additional, Kristeleit, Hartmut, additional, Lumsden, Graeme, additional, Macmillan, Craig, additional, MacPherson, Iain, additional, Malik, Zafar, additional, Mithal, Natasha, additional, Neal, Anthony, additional, Panwar, Udaiveer, additional, Proctor, Andrew, additional, Proctor, Steven John, additional, Raj, Sanjay, additional, Rehman, Shazza, additional, Sandri, Ines, additional, Scatchard, Kate, additional, Sherwin, Elizabeth, additional, Sims, Eliot, additional, Singer, Julian, additional, Smith, Sarah, additional, Tahir, Saad, additional, Taylor, Wendy, additional, Tsalic, Medy, additional, Verrill, Mark, additional, Wardley, Andrew, additional, Waters, Simon, additional, Wheatley, Duncan, additional, Wright, Kathryn, additional, Yuille, Frances, additional, Alonso, Isabel, additional, Artagaveytia, Nora, additional, Rodriguez, Robinson, additional, Arbona, Esther, additional, Garcia, Yuraima, additional, Lion, Lorena, additional, Marcano, Dalila, additional, and Van Thuan, Tran, additional

Published
2017
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11. Effects of lifestyle and diet as modifiers of risk of breast cancer (BC) in BRCA1 and BRCA2 carriers

Author

Marina Pollan, Asunción Torres, Teresa Ramon Y Cajal, Gemma Llort, Adela Castello, David Fisas, Carmen Yague, Consol Lopez, and Maria Teresa Leon

Subjects
Gerontology, Cancer Research, business.industry, Genetic counseling, Physical activity, Ethics committee, medicine.disease, Logistic regression, Penetrance, Lifestyle factors, Breast cancer, Oncology, Medicine, Lifetime risk, business, Demography
Abstract

1505 Background: Mutations in the BRCA1/2 genes confer a high lifetime risk of BC. Penetrance varies among populations and individuals suggesting that non-genetic factors may modify the inherited risk. Knowledge of modifiable factors will help to develop preventive strategies. Methods: Information on physical activity (PA) (current PA and in the adolescence) and smoking was collected in 892 women (W) with a BRCA1/BRCA2 germ-line mutation (582 with BC, 45,62% BRCA2) from 279 families, followed at three Spanish Genetic Counseling Units, 481of these W also answered a food frequency questionnaire. Participants gave their consent and the study was approved by the ethics committee. The association between BC, lifestyle factors and dietary patterns (Mediterranean and Western) associated with BC were studied using logistic regression. Huber-White robust estimators of variance were employed to take into account correlations between family members. Age, menopausal status, specific mutated gene, BMI, parity and oral contraception were included as co-variables. BC was classified as HR+/+,- or HR-. Results: W who did PA daily had half the risk of BC than sedentary W (OR:0,53;p=0,043 for current PA;OR:0,40;p=0,007 for PA in the adolescent) and no differences were observed between BRCA1 and BRCA2 carriers. Also, W who daily exercised in both periods had a reduction of their BC risk (OR:0,22;p

Published
2017
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