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Full-text held externally
- PMID: 22144499
- UKPMCID: 22144499
- DOI: 10.1158/1055-9965.EPI-11-0775
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Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
Mavaddat, Nasim; Barrowdale, Daniel; Andrulis, Irene L; Domchek, Susan M; Eccles, Diana; Nevanlinna, Heli; Ramus, Susan J; Spurdle, Amanda; Robson, Mark; Sherman, Mark; Mulligan, Anna Marie; Couch, Fergus J; Engel, Christoph; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga M; Southey, Melissa C; Terry, Mary Beth; Goldgar, David; O'Malley, Frances; John, Esther M; Janavicius, Ramunas; Tihomirova, Laima; Hansen, Thomas V O; Nielsen, Finn C; Osorio, Ana; Stavropoulou, Alexandra; BenÃtez, Javier; Manoukian, Siranoush; Peissel, Bernard; Barile, Monica; Volorio, Sara; Pasini, Barbara; Dolcetti, Riccardo; Putignano, Anna Laura; Ottini, Laura; Radice, Paolo; Hamann, Ute; Rashid, Muhammad U; Hogervorst, Frans B; Kriege, Mieke; van der Luijt, Rob B; ; Peock, Susan; Frost, Debra; Evans, D Gareth; Brewer, Carole; Walker, Lisa; Rogers, Mark T; Side, Lucy E; Houghton, Catherine; ; Weaver, JoEllen; Godwin, Andrew K; Schmutzler, Rita K; Wappenschmidt, Barbara; Meindl, Alfons; Kast, Karin; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Doroteha; Preisler-Adams, Sabine; Varon-Mateeva, Raymonda; Schönbuchner, Ines; Gevensleben, Heidrun; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Barjhoux, Laure; ; Isaacs, Claudine; Peshkin, Beth N; Caldes, Trinidad; de la Hoya, Miguel; Cañadas, Carmen; Heikkinen, Tuomas; Heikkilä, Päivi; Aittomäki, Kristiina; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Agnarsson, Bjarni A; Arason, Adalgeir; Barkardottir, Rosa B; Dumont, Martine; Simard, Jacques; Montagna, Marco; Agata, Simona; D'Andrea, Emma; Yan, Max; Fox, Stephen; ; Rebbeck, Timothy R; Rubinstein, Wendy; Tung, Nadine; Garber, Judy E; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S; Lindor, Noralane M; Szabo, Csilla; Offit, Kenneth; Sakr, Rita; Gaudet, Mia M; Singer, Christian F; Tea, Muy-Kheng; Rappaport, Christine; Mai, Phuong L; Greene, Mark H; Sokolenko, Anna; Imyanitov, Evgeny; Toland, Amanda Ewart; Senter, Leigha; Sweet, Kevin; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben; Caligo, Maria; Aretini, Paolo; Rantala, Johanna; von Wachenfeld, Anna; Henriksson, Karin; ; Steele, Linda; Neuhausen, Susan L; Nussbaum, Robert; Beattie, Mary; Odunsi, Kunle; Sucheston, Lara; Gayther, Simon A; Nathanson, Kate; Gross, Jenny; Walsh, Christine; Karlan, Beth; Chenevix-Trench, Georgia; Easton, Douglas F; Antoniou, Antonis C;
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012;21(1):134-47.
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Full-text held externally
- PMID: 22144499
- UKPMCID: 22144499
- DOI: 10.1158/1055-9965.EPI-11-0775
Abstract
BACKGROUND: Previously, 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. METHODS: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. RESULTS: There 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.
Bibliographic metadata
- Mavaddat, Nasim
- Barrowdale, Daniel
- Andrulis, Irene L
- Domchek, Susan M
- Eccles, Diana
- Nevanlinna, Heli
- Ramus, Susan J
- Spurdle, Amanda
- Robson, Mark
- Sherman, Mark
- Mulligan, Anna Marie
- Couch, Fergus J
- Engel, Christoph
- McGuffog, Lesley
- Healey, Sue
- Sinilnikova, Olga M
- Southey, Melissa C
- Terry, Mary Beth
- Goldgar, David
- O'Malley, Frances
- John, Esther M
- Janavicius, Ramunas
- Tihomirova, Laima
- Hansen, Thomas V O
- Nielsen, Finn C
- Osorio, Ana
- Stavropoulou, Alexandra
- BenÃtez, Javier
- Manoukian, Siranoush
- Peissel, Bernard
- Barile, Monica
- Volorio, Sara
- Pasini, Barbara
- Dolcetti, Riccardo
- Putignano, Anna Laura
- Ottini, Laura
- Radice, Paolo
- Hamann, Ute
- Rashid, Muhammad U
- Hogervorst, Frans B
- Kriege, Mieke
- van der Luijt, Rob B
- Peock, Susan
- Frost, Debra
- Evans, D Gareth
- Brewer, Carole
- Walker, Lisa
- Rogers, Mark T
- Side, Lucy E
- Houghton, Catherine
- Weaver, JoEllen
- Godwin, Andrew K
- Schmutzler, Rita K
- Wappenschmidt, Barbara
- Meindl, Alfons
- Kast, Karin
- Arnold, Norbert
- Niederacher, Dieter
- Sutter, Christian
- Deissler, Helmut
- Gadzicki, Doroteha
- Preisler-Adams, Sabine
- Varon-Mateeva, Raymonda
- Schönbuchner, Ines
- Gevensleben, Heidrun
- Stoppa-Lyonnet, Dominique
- Belotti, Muriel
- Barjhoux, Laure
- Isaacs, Claudine
- Peshkin, Beth N
- Caldes, Trinidad
- de la Hoya, Miguel
- Cañadas, Carmen
- Heikkinen, Tuomas
- Heikkilä, Päivi
- Aittomäki, Kristiina
- Blanco, Ignacio
- Lazaro, Conxi
- Brunet, Joan
- Agnarsson, Bjarni A
- Arason, Adalgeir
- Barkardottir, Rosa B
- Dumont, Martine
- Simard, Jacques
- Montagna, Marco
- Agata, Simona
- D'Andrea, Emma
- Yan, Max
- Fox, Stephen
- Rebbeck, Timothy R
- Rubinstein, Wendy
- Tung, Nadine
- Garber, Judy E
- Wang, Xianshu
- Fredericksen, Zachary
- Pankratz, Vernon S
- Lindor, Noralane M
- Szabo, Csilla
- Offit, Kenneth
- Sakr, Rita
- Gaudet, Mia M
- Singer, Christian F
- Tea, Muy-Kheng
- Rappaport, Christine
- Mai, Phuong L
- Greene, Mark H
- Sokolenko, Anna
- Imyanitov, Evgeny
- Toland, Amanda Ewart
- Senter, Leigha
- Sweet, Kevin
- Thomassen, Mads
- Gerdes, Anne-Marie
- Kruse, Torben
- Caligo, Maria
- Aretini, Paolo
- Rantala, Johanna
- von Wachenfeld, Anna
- Henriksson, Karin
- Steele, Linda
- Neuhausen, Susan L
- Nussbaum, Robert
- Beattie, Mary
- Odunsi, Kunle
- Sucheston, Lara
- Gayther, Simon A
- Nathanson, Kate
- Gross, Jenny
- Walsh, Christine
- Karlan, Beth
- Chenevix-Trench, Georgia
- Easton, Douglas F
- Antoniou, Antonis C
- Glendon, Gord
- Selander, Teresa
- Gill, Mona
- Collins, Lucine
- Weerasooriya, Nayana
- Ejlertsen, Bent
- Alonso, R M
- Pita, G
- Milne, R M
- Hogervorst, F B L
- Verhoef, S
- Verheus, M
- van 't Veer, L J
- van Leeuwen, F E
- Rookus, M A
- Collée, M
- van den Ouweland, A M W
- Jager, A
- Hooning, M J
- Tilanus-Linthorst, M M A
- Seynaeve, C
- van Asperen, C J
- Wijnen, J T
- Vreeswijk, M P
- Tollenaar, R A
- Devilee, P
- Ligtenberg, M J
- Hoogerbrugge, N
- Ausems, M J
- van der Luijt, R B
- Aalfs, C M
- van Os, T A
- Gille, J J P
- Waisfisz, Q
- Meijers-Heijboer, H E J
- Gomez-Garcia, E B
- van Roozendaal, C E
- Blok, Marinus J
- Caanen, B
- Oosterwijk, J C
- van der Hout, A H
- Mourits, M J
- Vasen, H F
- Peock, Susan
- Frost, Debra
- Ellis, Steve
- Fineberg, Elena
- Miedzybrodzka, Zosia
- Gregory, Helen
- Morrison, Patrick
- Jeffers, Lisa
- Cole, Trevor
- Ong, Kai-ren
- Hoffman, Jonathan
- Donaldson, Alan
- James, Margaret
- Paterson, Joan
- Downing, Sarah
- Taylor, Amy
- Murray, Alexandra
- Rogers, Mark T
- McCann, Emma
- Kennedy, M John
- Barton, David
- Porteous, Mary
- Drummond, Sarah
- Brewer, Carole
- Kivuva, Emma
- Searle, Anne
- Goodman, Selina
- Hill, Kathryn
- Davidson, Rosemarie
- Murday, Victoria
- Bradshaw, Nicola
- Snadden, Lesley
- Longmuir, Mark
- Watt, Catherine
- Gibson, Sarah
- Haque, Eshika
- Tobias, Ed
- Duncan, Alexis
- Izatt, Louise
- Jacobs, Chris
- Langman, Caroline
- Whaite, Anna
- Dorkins, Huw
- Barwell, Julian
- Adlard, Julian
- Chu, Carol
- Miller, Julie
- Ellis, Ian
- Houghton, Catherine
- Evans, D Gareth
- Lalloo, Fiona
- Taylor, Jane
- Side, Lucy
- Male, Alison
- Berlin, Cheryl
- Eason, Jacqueline
- Collier, Rebecca
- Douglas, Fiona
- Claber, Oonagh
- Jobson, Irene
- Walker, Lisa
- McLeod, Diane
- Halliday, Dorothy
- Durell, Sarah
- Stayner, Barbara
- Eeles, Ros
- Shanley, Susan
- Rahman, Nazneen
- Houlston, Richard
- Bancroft, Elizabeth
- D'Mello, Lucia
- Page, Elizabeth
- Ardern-Jones, Audrey
- Kelly, Kohut
- Wiggins, Jennifer
- Castro, Elena
- Mitra, Anita
- Robertson, Lisa
- Cook, Jackie
- Quarrell, Oliver
- Bardsley, Cathryn
- Hodgson, Shirley
- Goff, Sheila
- Brice, Glen
- Winchester, Lizzie
- Eddy, Charlotte
- Tripathi, Vishakha
- Attard, Virginia
- Eccles, Diana
- Lucassen, Anneke
- Crawford, Gillian
- McBride, Donna
- Smalley, Sarah
- Gilroy, M Pat
- Cruz, Lesley
- Faison, Diane
- Dettore, Barbara
- Donovan, Mary
- Butler, Meghan
- Sinilnikova, Olga
- Mazoyer, Sylvie
- Barjhoux, Laure
- Verny-Pierre, Carole
- Giraud, Sophie
- Léone, Mélanie
- Stoppa-Lyonnet, Dominique
- Gauthier-Villars, Marion
- Buecher, Bruno
- Houdayer, Claude
- Moncoutier, Virginie
- Belotti, Muriel
- Tirapo, Carole
- de Pauw, Antoine
- Bressac-de-Paillerets, Brigitte
- Remenieras, Audrey
- Byrde, Véronique
- Caron, Olivier
- Lenoir, Gilbert
- Bignon, Yves-Jean
- Uhrhammer, Nancy
- Lasset, Christine
- Bonadona, Valérie
- Hardouin, Agnès
- Berthet, Pascaline
- Sobol, Hagay
- Bourdon, Violaine
- Noguchi, Tetsuro
- Eisinger, François
- Coulet, Florence
- Colas, Chrystelle
- Soubrier, Florent
- Coupier, Isabelle
- Pujol, Pascal
- Peyrat, Jean-Philippe
- Fournier, Joëlle
- Révillion, Françoise
- Vennin, Philippe
- Adenis, Claude
- Rouleau, Etienne
- Lidereau, Rosette
- Demange, Liliane
- Nogues, Catherine
- Muller, Danièle
- Fricker, Jean-Pierre
- Longy, Michel
- Sevenet, Nicolas
- Toulas, Christine
- Guimbaud, Rosine
- Gladieff, Laurence
- Feillel, Viviane
- Leroux, Dominique
- Dreyfus, Hélène
- Rebischung, Christine
- Peysselon, Magalie
- Coron, Fanny
- Faivre, Laurence
- Prieur, Fabienne
- Lebrun, Marine
- Caroline, Kientz
- Ferrer, Sandra Fert
- Frénay, Marc
- Vénat-Bouvet, Laurence
- Delnatte, Capucine
- Mortemousque, Isabelle
- Lynch, Henry T
- Snyder, Carrie L
- Aaltonen, Kirsimari
- Blomqvist, Carl
- Erkkilä, Irja
- Tranchant, Martine
- Simard, J
- Thorne, Heather
- Niedermayr, Eveline
- Borg, Ake
- Loman, Niklas
- Olsson, HÃ¥kan
- Kristoffersson, Ulf
- Jernström, Helena
- Harbst, Katja
- Henriksson, Karin
- Lindblom, Annika
- Arver, Brita
- von Wachenfeldt, Anna
- Liljegren, Annelie
- Barbany-Bustinza, Gisela
- Rantala, Johanna
- Pharoah, Paul
- Pye, Carole
- Harrington, Patricia
- Wozniak, Evan
- Moysich, Kirsten
- 5U01CA113916, NCI NIH HHS, United States
- A11174, Cancer Research UK, United Kingdom
- C12292/A11174, Cancer Research UK, United Kingdom
- C1287/A10118, Cancer Research UK, United Kingdom
- C1287/A11990, Cancer Research UK, United Kingdom
- C5047/A8385, Cancer Research UK, United Kingdom
- CA116167, NCI NIH HHS, United States
- CA116201, NCI NIH HHS, United States
- CA128978, NCI NIH HHS, United States
- CA74415, NCI NIH HHS, United States
- N02PC45022-46, NCI NIH HHS, United States
- P30 CA51008-12, NCI NIH HHS, United States
- P50 CA116201, NCI NIH HHS, United States
- P50-CA058207, NCI NIH HHS, United States
- R01 CA106588-09, NCI NIH HHS, United States
- R01 CA122340, NCI NIH HHS, United States
- R01 CA128978, NCI NIH HHS, United States
- R01 CA140323, NCI NIH HHS, United States
- R01 CA140323-03, NCI NIH HHS, United States
- RFA CA- 06-503, NCI NIH HHS, United States
- RFA-CA-06-503, NCI NIH HHS, United States
- U01 CA69398, NCI NIH HHS, United States
- U01 CA69417, NCI NIH HHS, United States
- U01 CA69446, NCI NIH HHS, United States
- U01 CA69467, NCI NIH HHS, United States
- U01 CA69631, NCI NIH HHS, United States
- U01 CA69638, NCI NIH HHS, United States
- U01CA69631, NCI NIH HHS, United States
- , Canadian Institutes of Health Research, Canada
- , Medical Research Council, United Kingdom