Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA)

Nasim Mavaddat, Daniel Barrowdale, Irene L. Andrulis, Susan M. Domchek, Diana Eccles, Heli Nevanlinna, Susan J. Ramus, Amanda Spurdle, Mark Robson, Mark E. Sherman, Anna Marie Mulligan, Fergus J Couch, Christoph Engel, Lesley McGuffog, Sue Healey, Olga M. Sinilnikova, Melissa C. Southey, Mary Beth Terry, David Goldgar, Frances O'MalleyEsther M. John, Ramunas Janavicius, Laima Tihomirova, Thomas V O Hansen, Finn C. Nielsen, Ana Osorio, Alexandra Stavropoulou, Javier Benítez, Siranoush Manoukian, Bernard Peissel, Monica Barile, Sara Volorio, Barbara Pasini, Riccardo Dolcetti, Anna Laura Putignano, Laura Ottini, Paolo Radice, Ute Hamann, Muhammad U. Rashid, Frans B. Hogervorst, Mieke Kriege, Rob B. Van Der Luijt, Susan Peock, Debra Frost, D. Gareth Evans, Carole Brewer, Lisa Walker, Mark T. Rogers, Lucy E. Side, Catherine Houghton, JoEllen Weaver, Andrew K. Godwin, Rita K. Schmutzler, Barbara Wappenschmidt, Alfons Meindl, Karin Kast, Norbert Arnold, Dieter Niederacher, Christian Sutter, Helmut Deissler, Doroteha Gadzicki, Sabine Preisler-Adams, Raymonda Varon-Mateeva, Ines Schönbuchner, Heidrun Gevensleben, Dominique Stoppa-Lyonnet, Muriel Belotti, Laure Barjhoux, Claudine Isaacs, Beth N. Peshkin, Trinidad Caldes, Miguel De Al Hoya, Carmen Cañadas, Tuomas Heikkinen, Päivi Heikkilä, Kristiina Aittomäki, Ignacio Blanco, Conxi Lazaro, Joan Brunet, Bjarni A. Agnarsson, Adalgeir Arason, Rosa B. Barkardottir, Martine Dumont, Jacques Simard, Marco Montagna, Simona Agata, Emma D'Andrea, Max Yan, Stephen Fox, Timothy R. Rebbeck, Wendy Rubinstein, Nadine Tung, Judy E. Garber, Xianshu Wang, Zachary Fredericksen, Vernon S. Pankratz, Noralane Morey Lindor, Csilla Szabo, Kenneth Offit, Rita Sakr, Mia M. Gaudet, Christian F. Singer, Muy Kheng Tea, Christine Rappaport, Phuong L. Mai, Mark H. Greene, Anna Sokolenko, Evgeny Imyanitov, Amanda Ewart Toland, Leigha Senter, Kevin Sweet, Mads Thomassen, Anne Marie Gerdes, Torben Kruse, Maria Caligo, Paolo Aretini, Johanna Rantala, Anna Von Wachenfeld, Karin Henriksson, Linda Steele, Susan L. Neuhausen, Robert Nussbaum, Mary Beattie, Kunle Odunsi, Lara Sucheston, Simon A. Gayther, Kate Nathanson, Jenny Gross, Christine Walsh, Beth Karlan, Georgia Chenevix-Trench, Douglas F. Easton, Antonis C. Antoniou

Research output: Contribution to journalArticle

259 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)134-147
Number of pages14
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number1
DOIs
StatePublished - Jan 2012

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Estrogen Receptors
Ovarian Neoplasms
Research Personnel
Pathology
Breast Neoplasms
Mutation
Odds Ratio
Neoplasms
Progesterone Receptors
Brain Stem Neoplasms
Breast

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

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 E.; 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; Benítez, 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 Al 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 Morey; 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.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 1, 01.2012, p. 134-147.

Research output: Contribution to journalArticle

Mavaddat, N, Barrowdale, D, Andrulis, IL, Domchek, SM, Eccles, D, Nevanlinna, H, Ramus, SJ, Spurdle, A, Robson, M, Sherman, ME, Mulligan, AM, Couch, FJ, Engel, C, McGuffog, L, Healey, S, Sinilnikova, OM, Southey, MC, Terry, MB, Goldgar, D, O'Malley, F, John, EM, Janavicius, R, Tihomirova, L, Hansen, TVO, Nielsen, FC, Osorio, A, Stavropoulou, A, Benítez, J, Manoukian, S, Peissel, B, Barile, M, Volorio, S, Pasini, B, Dolcetti, R, Putignano, AL, Ottini, L, Radice, P, Hamann, U, Rashid, MU, Hogervorst, FB, Kriege, M, Van Der Luijt, RB, Peock, S, Frost, D, Evans, DG, Brewer, C, Walker, L, Rogers, MT, Side, LE, Houghton, C, Weaver, J, Godwin, AK, Schmutzler, RK, Wappenschmidt, B, Meindl, A, Kast, K, Arnold, N, Niederacher, D, Sutter, C, Deissler, H, Gadzicki, D, Preisler-Adams, S, Varon-Mateeva, R, Schönbuchner, I, Gevensleben, H, Stoppa-Lyonnet, D, Belotti, M, Barjhoux, L, Isaacs, C, Peshkin, BN, Caldes, T, De Al Hoya, M, Cañadas, C, Heikkinen, T, Heikkilä, P, Aittomäki, K, Blanco, I, Lazaro, C, Brunet, J, Agnarsson, BA, Arason, A, Barkardottir, RB, Dumont, M, Simard, J, Montagna, M, Agata, S, D'Andrea, E, Yan, M, Fox, S, Rebbeck, TR, Rubinstein, W, Tung, N, Garber, JE, Wang, X, Fredericksen, Z, Pankratz, VS, Lindor, NM, Szabo, C, Offit, K, Sakr, R, Gaudet, MM, Singer, CF, Tea, MK, Rappaport, C, Mai, PL, Greene, MH, Sokolenko, A, Imyanitov, E, Toland, AE, Senter, L, Sweet, K, Thomassen, M, Gerdes, AM, Kruse, T, Caligo, M, Aretini, P, Rantala, J, Von Wachenfeld, A, Henriksson, K, Steele, L, Neuhausen, SL, Nussbaum, R, Beattie, M, Odunsi, K, Sucheston, L, Gayther, SA, Nathanson, K, Gross, J, Walsh, C, Karlan, B, Chenevix-Trench, G, Easton, DF & Antoniou, AC 2012, 'Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA)', Cancer Epidemiology Biomarkers and Prevention, vol. 21, no. 1, pp. 134-147. https://doi.org/10.1158/1055-9965.EPI-11-0775
Mavaddat, Nasim ; Barrowdale, Daniel ; Andrulis, Irene L. ; Domchek, Susan M. ; Eccles, Diana ; Nevanlinna, Heli ; Ramus, Susan J. ; Spurdle, Amanda ; Robson, Mark ; Sherman, Mark E. ; 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 ; Benítez, 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 Al 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 Morey ; 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. / Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers : Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA). In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 1. pp. 134-147.
@article{b7531191153f43ffa4a6c0804dc9cf36,
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)",
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.",
author = "Nasim Mavaddat and Daniel Barrowdale and Andrulis, {Irene L.} and Domchek, {Susan M.} and Diana Eccles and Heli Nevanlinna and Ramus, {Susan J.} and Amanda Spurdle and Mark Robson and Sherman, {Mark E.} and Mulligan, {Anna Marie} and Couch, {Fergus J} and Christoph Engel and Lesley McGuffog and Sue Healey and Sinilnikova, {Olga M.} and Southey, {Melissa C.} and Terry, {Mary Beth} and David Goldgar and Frances O'Malley and John, {Esther M.} and Ramunas Janavicius and Laima Tihomirova and Hansen, {Thomas V O} and Nielsen, {Finn C.} and Ana Osorio and Alexandra Stavropoulou and Javier Ben{\'i}tez and Siranoush Manoukian and Bernard Peissel and Monica Barile and Sara Volorio and Barbara Pasini and Riccardo Dolcetti and Putignano, {Anna Laura} and Laura Ottini and Paolo Radice and Ute Hamann and Rashid, {Muhammad U.} and Hogervorst, {Frans B.} and Mieke Kriege and {Van Der Luijt}, {Rob B.} and Susan Peock and Debra Frost and Evans, {D. Gareth} and Carole Brewer and Lisa Walker and Rogers, {Mark T.} and Side, {Lucy E.} and Catherine Houghton and JoEllen Weaver and Godwin, {Andrew K.} and Schmutzler, {Rita K.} and Barbara Wappenschmidt and Alfons Meindl and Karin Kast and Norbert Arnold and Dieter Niederacher and Christian Sutter and Helmut Deissler and Doroteha Gadzicki and Sabine Preisler-Adams and Raymonda Varon-Mateeva and Ines Sch{\"o}nbuchner and Heidrun Gevensleben and Dominique Stoppa-Lyonnet and Muriel Belotti and Laure Barjhoux and Claudine Isaacs and Peshkin, {Beth N.} and Trinidad Caldes and {De Al Hoya}, Miguel and Carmen Ca{\~n}adas and Tuomas Heikkinen and P{\"a}ivi Heikkil{\"a} and Kristiina Aittom{\"a}ki and Ignacio Blanco and Conxi Lazaro and Joan Brunet and Agnarsson, {Bjarni A.} and Adalgeir Arason and Barkardottir, {Rosa B.} and Martine Dumont and Jacques Simard and Marco Montagna and Simona Agata and Emma D'Andrea and Max Yan and Stephen Fox and Rebbeck, {Timothy R.} and Wendy Rubinstein and Nadine Tung and Garber, {Judy E.} and Xianshu Wang and Zachary Fredericksen and Pankratz, {Vernon S.} and Lindor, {Noralane Morey} and Csilla Szabo and Kenneth Offit and Rita Sakr and Gaudet, {Mia M.} and Singer, {Christian F.} and Tea, {Muy Kheng} and Christine Rappaport and Mai, {Phuong L.} and Greene, {Mark H.} and Anna Sokolenko and Evgeny Imyanitov and Toland, {Amanda Ewart} and Leigha Senter and Kevin Sweet and Mads Thomassen and Gerdes, {Anne Marie} and Torben Kruse and Maria Caligo and Paolo Aretini and Johanna Rantala and {Von Wachenfeld}, Anna and Karin Henriksson and Linda Steele and Neuhausen, {Susan L.} and Robert Nussbaum and Mary Beattie and Kunle Odunsi and Lara Sucheston and Gayther, {Simon A.} and Kate Nathanson and Jenny Gross and Christine Walsh and Beth Karlan and Georgia Chenevix-Trench and Easton, {Douglas F.} and Antoniou, {Antonis C.}",
year = "2012",
month = "1",
doi = "10.1158/1055-9965.EPI-11-0775",
language = "English (US)",
volume = "21",
pages = "134--147",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

TY - JOUR

T1 - Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers

T2 - Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA)

AU - Mavaddat, Nasim

AU - Barrowdale, Daniel

AU - Andrulis, Irene L.

AU - Domchek, Susan M.

AU - Eccles, Diana

AU - Nevanlinna, Heli

AU - Ramus, Susan J.

AU - Spurdle, Amanda

AU - Robson, Mark

AU - Sherman, Mark E.

AU - Mulligan, Anna Marie

AU - Couch, Fergus J

AU - Engel, Christoph

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Sinilnikova, Olga M.

AU - Southey, Melissa C.

AU - Terry, Mary Beth

AU - Goldgar, David

AU - O'Malley, Frances

AU - John, Esther M.

AU - Janavicius, Ramunas

AU - Tihomirova, Laima

AU - Hansen, Thomas V O

AU - Nielsen, Finn C.

AU - Osorio, Ana

AU - Stavropoulou, Alexandra

AU - Benítez, Javier

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Barile, Monica

AU - Volorio, Sara

AU - Pasini, Barbara

AU - Dolcetti, Riccardo

AU - Putignano, Anna Laura

AU - Ottini, Laura

AU - Radice, Paolo

AU - Hamann, Ute

AU - Rashid, Muhammad U.

AU - Hogervorst, Frans B.

AU - Kriege, Mieke

AU - Van Der Luijt, Rob B.

AU - Peock, Susan

AU - Frost, Debra

AU - Evans, D. Gareth

AU - Brewer, Carole

AU - Walker, Lisa

AU - Rogers, Mark T.

AU - Side, Lucy E.

AU - Houghton, Catherine

AU - Weaver, JoEllen

AU - Godwin, Andrew K.

AU - Schmutzler, Rita K.

AU - Wappenschmidt, Barbara

AU - Meindl, Alfons

AU - Kast, Karin

AU - Arnold, Norbert

AU - Niederacher, Dieter

AU - Sutter, Christian

AU - Deissler, Helmut

AU - Gadzicki, Doroteha

AU - Preisler-Adams, Sabine

AU - Varon-Mateeva, Raymonda

AU - Schönbuchner, Ines

AU - Gevensleben, Heidrun

AU - Stoppa-Lyonnet, Dominique

AU - Belotti, Muriel

AU - Barjhoux, Laure

AU - Isaacs, Claudine

AU - Peshkin, Beth N.

AU - Caldes, Trinidad

AU - De Al Hoya, Miguel

AU - Cañadas, Carmen

AU - Heikkinen, Tuomas

AU - Heikkilä, Päivi

AU - Aittomäki, Kristiina

AU - Blanco, Ignacio

AU - Lazaro, Conxi

AU - Brunet, Joan

AU - Agnarsson, Bjarni A.

AU - Arason, Adalgeir

AU - Barkardottir, Rosa B.

AU - Dumont, Martine

AU - Simard, Jacques

AU - Montagna, Marco

AU - Agata, Simona

AU - D'Andrea, Emma

AU - Yan, Max

AU - Fox, Stephen

AU - Rebbeck, Timothy R.

AU - Rubinstein, Wendy

AU - Tung, Nadine

AU - Garber, Judy E.

AU - Wang, Xianshu

AU - Fredericksen, Zachary

AU - Pankratz, Vernon S.

AU - Lindor, Noralane Morey

AU - Szabo, Csilla

AU - Offit, Kenneth

AU - Sakr, Rita

AU - Gaudet, Mia M.

AU - Singer, Christian F.

AU - Tea, Muy Kheng

AU - Rappaport, Christine

AU - Mai, Phuong L.

AU - Greene, Mark H.

AU - Sokolenko, Anna

AU - Imyanitov, Evgeny

AU - Toland, Amanda Ewart

AU - Senter, Leigha

AU - Sweet, Kevin

AU - Thomassen, Mads

AU - Gerdes, Anne Marie

AU - Kruse, Torben

AU - Caligo, Maria

AU - Aretini, Paolo

AU - Rantala, Johanna

AU - Von Wachenfeld, Anna

AU - Henriksson, Karin

AU - Steele, Linda

AU - Neuhausen, Susan L.

AU - Nussbaum, Robert

AU - Beattie, Mary

AU - Odunsi, Kunle

AU - Sucheston, Lara

AU - Gayther, Simon A.

AU - Nathanson, Kate

AU - Gross, Jenny

AU - Walsh, Christine

AU - Karlan, Beth

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F.

AU - Antoniou, Antonis C.

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

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U2 - 10.1158/1055-9965.EPI-11-0775

DO - 10.1158/1055-9965.EPI-11-0775

M3 - Article

C2 - 22144499

AN - SCOPUS:84862907494

VL - 21

SP - 134

EP - 147

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 1

ER -