Citations 2
Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel
Yerushalmi, Rinat , Yablonski‐Peretz, Tamar, Wang, Qin , Bolla, Manjeet K. , Michailidou, Kyriaki , Ahearn, Thomas U. , Andrulis, Irene L. , Antoniou, Antonis C. , Auvinen, Päivi , Freeman, Laura Beane, Beckmann, Matthias W. , Bermisheva, Marina , Bodelón, Clara , Bogdanova, Natalia , Bojesen, Stig E. , Byers, Helen, Camp, Nicola J. , Chang‐Claude, Jenny , Chirlaque, María‐Dolores , Collaborators, NBCS, Collée, Margriet J., Dörk, Thilo , Eccles, Diana , Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Goldberg, Mark S. , Guénel, Pascal , Hamann, Ute, He, Wei , Hillemanns, Peter , Hoppe, Reiner , Hopper, John L. , Investigators, ABCTB, Jakovchevska, Simona, John, Esther M. , Johnson, Nichola , Jones, Michael E. , Kristensen, Vessela N. , Kurian, Allison W. , Lambrechts, Diether , Lejbkowicz, Flavio, Lindblom, Annika , Loibl, Sibylle , Lori, Adriana , Mannermaa, Arto, Manoochehri, Mehdi, Mavroudis, Dimitrios, Menon, Usha , Nevelsteen, Ines, Obi, Nadia , Offit, Ken, Plaseska‐Karanfilska, Dijana , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Rack, Brigitte , Rhenius, Valerie , Romero, Atocha , Schwentner, Lukas , Shah, Mitul , Stone, Jennifer , Taylor, Jack A. , Kolk, Lizet E. van der, Wendt, Camilla, Yang, Xiaohong R. , Zheng, Wei , Pharoah, Paul D.P. , Easton, Douglas F. , Ben-Sachar, Shay, Elefant, Naama , Shamir, Ron , Elkon, Ran , Lambrechts, Diether , Michailidou, Kyriaki , Antoniou, Antonis C , Devilee, Peter , Eccles, Diana , Newman, William G , Radice, Paolo , Elkon, Ran , Dörk, Thilo , Lambrechts, Diether , Hillemanns, Peter , Pharoah, Paul D P , Menon, Usha , Evans, D Gareth , John, Esther M , Jones, Michael E , Lambrechts, Diether , Guénel, Pascal , Romero, Atocha , García-Closas, Montserrat , Bogdanova, Natalia V , Taylor, Jack A , Zheng, Wei , Kurian, Allison W , Stone, Jennifer , Bojesen, Stig E , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Levi, Hagai , Carmi, Shai , Rosset, Saharon , Zick, Aviad , Dennis, Joe , Lush, Michael J. , Anton‐Culver, Hoda , Arndt, Volker , Augustinsson, Annelie , Behrens, Sabine , Brenner, Hermann , Castelao, Jose E. , Chung, Wendy K. , Clarke, Christine L. , Collaborators, NBCS, Collée, Margriet , Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Daly, Mary Beryl , Devilee, Peter , Dossus, Laure , Eliassen, A. Heather , Eriksson, Mikael , Fletcher, Olivia , Fritschi, Lin , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Giles, Graham G. , Hall, Per N , Hollestelle, Antoinette , Investigators, ABCTB, Jakubowska, Anna , Jernström, Helena , Vijai, Joseph , Kaaks, Rudolf , Хуснутдинова, Э. К. , Kitahara, Cari M. , Koutros, Stella , Lacey, James V. , Marchand, Loı̈c Le , Lubiński, Jan , Mannermaa, Arto, Mulligan, Anna Marie , Murphy, Rachel A. , Newman, William G. , O’Brien, Katie M. , Olshan, Andrew F. , Olson, Janet E. , Panico, Salvatore , Peterlongo, Paolo , Radice, Paolo , Rennert, Gad , Saloustros, Emmanouil , Sandler, Dale P. , Schmidt, Marjanka K. , Sharma, Priyanka , Simard, Jacques , Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Toland, Amanda Ewart , Troester, Melissa A. , Truong, Thérèse , Weinberg, Clarice R. , Ziogas, Argyrios , Dunning, Alison M.
Journal of Medical Genetics | July 14, 2023 | Volume: 60 | Issue: 12 | Pages: 1186-1197
Background Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women. Methods We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel. Results In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28). Conclusions Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.
Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial
Gounder, Mrinal M. , Razak, Albiruni Abdul , Somaiah, Neeta , Chawla, Sant P. , Martín‐Broto, Javier , Schuetze, Scott M. , Vincenzi, Bruno , Wagner, Andrew J. , Chmielowski, Bartosz , Jones, Robin L. , Riedel, Richard F. , Stacchiotti, Silvia , Ganjoo, Kristen N. , Cesne, Axel Le , Italiano, Antoîne , Ryan, Christopher W. , Mulcahy, Mary F. , Forscher, Charles, Okuno, Scott H. , Hartner, Lee , Philip, Tony , Alcindor, Thierry , Reichardt, Peter , Chevreau, Christine , Morales, Claudia Maria Valverde, Chen, James L. , Deshpande, Hari A. , Nicholas, Garth , Gröschel, Stefan , Hatcher, Helen, Duffaud, Florence , Beveridge, Roberto Díaz, Meyer, Christian F. , Götze, Katharina S. , Mazzeo, F , Yakobson, Alexander, Zick, Aviad , Lee, Alexander T.J. , Estival, Anna , Napolitano, Andrea , Dickson, Mark A. , Michel, Dayana , Meng, Changting , Ben‐Shahar, Osnat , Chang, Hua, Landesman, Yosef , Shah, Jatin J., Shacham, Sharon, Kauffman, Michael , Attia, Steven , Schuetze, Scott M , Vincenzi, Bruno , Wagner, Andrew J , Chmielowski, Bartosz , Jones, Robin L , Riedel, Richard F , Loggers, Elizabeth T , Le Cesne, Axel , Italiano, Antoine , Garcia Del Muro, Xavier , Mulcahy, Mary F , Penel, Nicolas , Okuno, Scott , Elias, Anthony D , Hartner, Lee , Philip, Tony , Alcindor, Thierry , Lapeire, Lore , Blay, Jean-Yves , Chen, James L , Davis, Elizabeth J , Hatcher, Helen , Meyer, Christian , von Mehren, Margaret , Van Tine, Brian A , Götze, Katharina , Mazzeo, Filomena , Zick, Aviad , Lee, Alexander , Gonzalez, Anna Estival , Napolitano, Andrea , Michel, Dayana , Meng, Changting , Ben-Shahar, Osnat , Van Domelen, Dane R , Grignani, Giovanni , Burgess, Melissa , Piperno‐Neumann, Sophie , Elias, Anthony , Kasper, Bernd , Blay, Jean‐Yves , Schwartz, Gary K. , Davis, Elizabeth J. , Casado, Antonio , Badalamenti, Giuseppe , Eriksson, Mikael , Mehren, Margaret von , Tine, Brian A. Van , Li, Lingling , Liu, Jianjun , Walker, Christopher James
Journal of Clinical Oncology | April 8, 2022 | Volume: 40 | Issue: 22 | Pages: 2479-2490
PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461 ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.