%0 Journal Article %1 Mavaddat.2012 %A Mavaddat, Nasim %A Barrowdale, Daniel %A Andrulis, Irene L. %A Domchek, Susan M. %A Eccles, Diana %A Nevanlinna, Heli %A Ramus, Susan J. %A Spurdle, Amanda %A Robson, Mark %A Sherman, Mark %A Mulligan, Anna Marie %A Couch, Fergus J. %A Engel, Christoph %A McGuffog, Lesley %A Healey, Sue %A Sinilnikova, Olga M. %A Southey, Melissa C. %A Terry, Mary Beth %A Goldgar, David %A O'Malley, Frances %A John, Esther M. %A Janavicius, Ramunas %A Tihomirova, Laima %A Hansen, Thomas V O, %A Nielsen, Finn C. %A Osorio, Ana %A Stavropoulou, Alexandra %A Benítez, Javier %A Manoukian, Siranoush %A Peissel, Bernard %A Barile, Monica %A Volorio, Sara %A Pasini, Barbara %A Dolcetti, Riccardo %A Putignano, Anna Laura %A Ottini, Laura %A Radice, Paolo %A Hamann, Ute %A Rashid, Muhammad U. %A Hogervorst, Frans B. %A Kriege, Mieke %A van der Luijt, Rob B, %A Peock, Susan %A Frost, Debra %A Evans, D. Gareth %A Brewer, Carole %A Walker, Lisa %A Rogers, Mark T. %A Side, Lucy E. %A Houghton, Catherine %A Weaver, Joellen %A Godwin, Andrew K. %A Schmutzler, Rita K. %A Wappenschmidt, Barbara %A Meindl, Alfons %A Kast, Karin %A Arnold, Norbert %A Niederacher, Dieter %A Sutter, Christian %A Deissler, Helmut %A Gadzicki, Doroteha %A Preisler-Adams, Sabine %A Varon-Mateeva, Raymonda %A Schönbuchner, Ines %A Gevensleben, Heidrun %A Stoppa-Lyonnet, Dominique %A Belotti, Muriel %A Barjhoux, Laure %A Isaacs, Claudine %A Peshkin, Beth N. %A Caldes, Trinidad %A de la Hoya, Miguel, %A Cañadas, Carmen %A Heikkinen, Tuomas %A Heikkilä, Päivi %A Aittomäki, Kristiina %A Blanco, Ignacio %A Lazaro, Conxi %A Brunet, Joan %A Agnarsson, Bjarni A. %A Arason, Adalgeir %A Barkardottir, Rosa B. %A Dumont, Martine %A Simard, Jacques %A Montagna, Marco %A Agata, Simona %A D'Andrea, Emma %A Yan, Max %A Fox, Stephen %A Rebbeck, Timothy R. %A Rubinstein, Wendy %A Tung, Nadine %A Garber, Judy E. %A Wang, Xianshu %A Fredericksen, Zachary %A Pankratz, Vernon S. %A Lindor, Noralane M. %A Szabo, Csilla %A Offit, Kenneth %A Sakr, Rita %A Gaudet, Mia M. %A Singer, Christian F. %A Tea, Muy-Kheng %A Rappaport, Christine %A Mai, Phuong L. %A Greene, Mark H. %A Sokolenko, Anna %A Imyanitov, Evgeny %A Toland, Amanda Ewart %A Senter, Leigha %A Sweet, Kevin %A Thomassen, Mads %A Gerdes, Anne-Marie %A Kruse, Torben %A Caligo, Maria %A Aretini, Paolo %A Rantala, Johanna %A Wachenfeld, Anna von %A Henriksson, Karin %A Steele, Linda %A Neuhausen, Susan L. %A Nussbaum, Robert %A Beattie, Mary %A Odunsi, Kunle %A Sucheston, Lara %A Gayther, Simon A. %A Nathanson, Kate %A Gross, Jenny %A Walsh, Christine %A Karlan, Beth %A Chenevix-Trench, Georgia %A Easton, Douglas F. %A Antoniou, Antonis C. %D 2012 %J Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology %K Adult Aged Breast_Neoplasms/genetics/pathology Female Genes,_BRCA1 Genes,_BRCA2 Genetic_Predisposition_to_Disease Germ-Line_Mutation Humans Middle_Aged Neoplasm_Grading Ovarian_Neoplasms/genetics/pathology %N 1 %P 134–147 %T Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) %V 21 %X BACKGROUND\r\nPreviously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization.\r\nMETHODS\r\nWe used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers.\r\nRESULTS\r\nThere was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 × 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 × 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status ER-positive odds ratio (OR) for BRCA2 = 9.4, 95\% CI: 7.0-12.6 and PR-positive OR = 1.7, 95\% CI: 1.3-2.3, under joint analysis. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95\% CI: 2.4-4.4; P = 4.4 × 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95\% CI: 0.18-0.35; P = 2.3 × 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67\%; mucinous: 1\%; endometrioid: 12\%; clear-cell: 2\%). CONCLUSIONS/IMPACT: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis.

@article{Mavaddat.2012, abstract = {BACKGROUND\r\nPreviously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization.\r\nMETHODS\r\nWe used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers.\r\nRESULTS\r\nThere was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 × 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 × 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95\% CI: 7.0-12.6 and PR-positive OR = 1.7, 95\% CI: 1.3-2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95\% CI: 2.4-4.4; P = 4.4 × 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95\% CI: 0.18-0.35; P = 2.3 × 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67\%; mucinous: 1\%; endometrioid: 12\%; clear-cell: 2\%). CONCLUSIONS/IMPACT: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis.}, added-at = {2014-10-13T18:24:55.000+0200}, author = {Mavaddat, Nasim and Barrowdale, Daniel and Andrulis, Irene L. and Domchek, Susan M. and Eccles, Diana and Nevanlinna, Heli and Ramus, Susan J. and Spurdle, Amanda and Robson, Mark and Sherman, Mark and Mulligan, Anna Marie and Couch, Fergus J. and Engel, Christoph and McGuffog, Lesley and Healey, Sue and Sinilnikova, Olga M. and Southey, Melissa C. and Terry, Mary Beth and Goldgar, David and O'Malley, Frances and John, Esther M. and Janavicius, Ramunas and Tihomirova, Laima and {Hansen, Thomas V O} and Nielsen, Finn C. and Osorio, Ana and Stavropoulou, Alexandra and Benítez, Javier and Manoukian, Siranoush and Peissel, Bernard and Barile, Monica and Volorio, Sara and Pasini, Barbara and Dolcetti, Riccardo and Putignano, Anna Laura and Ottini, Laura and Radice, Paolo and Hamann, Ute and Rashid, Muhammad U. and Hogervorst, Frans B. and Kriege, Mieke and {van der Luijt, Rob B} and Peock, Susan and Frost, Debra and Evans, D. Gareth and Brewer, Carole and Walker, Lisa and Rogers, Mark T. and Side, Lucy E. and Houghton, Catherine and Weaver, Joellen and Godwin, Andrew K. and Schmutzler, Rita K. and Wappenschmidt, Barbara and Meindl, Alfons and Kast, Karin and Arnold, Norbert and Niederacher, Dieter and Sutter, Christian and Deissler, Helmut and Gadzicki, Doroteha and Preisler-Adams, Sabine and Varon-Mateeva, Raymonda and Schönbuchner, Ines and Gevensleben, Heidrun and Stoppa-Lyonnet, Dominique and Belotti, Muriel and Barjhoux, Laure and Isaacs, Claudine and Peshkin, Beth N. and Caldes, Trinidad and {de la Hoya, Miguel} and Cañadas, Carmen and Heikkinen, Tuomas and Heikkilä, Päivi and Aittomäki, Kristiina and Blanco, Ignacio and Lazaro, Conxi and Brunet, Joan and Agnarsson, Bjarni A. and Arason, Adalgeir and Barkardottir, Rosa B. and Dumont, Martine and Simard, Jacques and Montagna, Marco and Agata, Simona and D'Andrea, Emma and Yan, Max and Fox, Stephen and Rebbeck, Timothy R. and Rubinstein, Wendy and Tung, Nadine and Garber, Judy E. and Wang, Xianshu and Fredericksen, Zachary and Pankratz, Vernon S. and Lindor, Noralane M. and Szabo, Csilla and Offit, Kenneth and Sakr, Rita and Gaudet, Mia M. and Singer, Christian F. and Tea, Muy-Kheng and Rappaport, Christine and Mai, Phuong L. and Greene, Mark H. and Sokolenko, Anna and Imyanitov, Evgeny and Toland, Amanda Ewart and Senter, Leigha and Sweet, Kevin and Thomassen, Mads and Gerdes, Anne-Marie and Kruse, Torben and Caligo, Maria and Aretini, Paolo and Rantala, Johanna and Wachenfeld, Anna von and Henriksson, Karin and Steele, Linda and Neuhausen, Susan L. and Nussbaum, Robert and Beattie, Mary and Odunsi, Kunle and Sucheston, Lara and Gayther, Simon A. and Nathanson, Kate and Gross, Jenny and Walsh, Christine and Karlan, Beth and Chenevix-Trench, Georgia and Easton, Douglas F. and Antoniou, Antonis C.}, biburl = {https://www.bibsonomy.org/bibtex/2ac3d15478d687fcc7c41003a54cac37e/drtester}, interhash = {8db57b5f3309dfec2b7867477f8c52ab}, intrahash = {ac3d15478d687fcc7c41003a54cac37e}, journal = {Cancer epidemiology, biomarkers \& prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, keywords = {Adult Aged Breast_Neoplasms/genetics/pathology Female Genes,_BRCA1 Genes,_BRCA2 Genetic_Predisposition_to_Disease Germ-Line_Mutation Humans Middle_Aged Neoplasm_Grading Ovarian_Neoplasms/genetics/pathology}, number = 1, pages = {134–147}, timestamp = {2014-10-13T18:24:55.000+0200}, title = {Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)}, volume = 21, year = 2012 }