PortalPublikationenRefined histopathological predictors of BRCA1 and BRCA2 muta...

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Standard

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia. / Spurdle, Amanda B; Couch, Fergus J; Parsons, Michael T; McGuffog, Lesley; Barrowdale, Daniel; Bolla, Manjeet K; Wang, Qin; Healey, Sue; Schmutzler, Rita; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hansjoerg; Niederacher, Dieter; Sutter, Christian; Wang-Gohrke, Shan; Steinemann, Doris; Preisler-Adams, Sabine; Kast, Karin; Varon-Mateeva, Raymonda; Ellis, Steve; Frost, Debra; Platte, Radka; Perkins, Jo; Evans, D; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Cole, Trevor; Scuvera, Giulietta; Manoukian, Siranoush; Bonanni, Bernardo; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Pasini, Barbara; Papi, Laura; Varesco, Liliana; Balleine, Rosemary; Nathanson, Katherine L; Domchek, Susan M; Offitt, Kenneth; Jakubowska, Anna; Lindor, Noralane; Thomassen, Mads; Jensen, Uffe; Rantala, Johanna; Borg, Åke; Andrulis, Irene L; Miron, Alexander; Hansen, Thomas; Caldes, Trinidad; Neuhausen, Susan L; Toland, Amanda E; Nevanlinna, Heli; Montagna, Marco; Garber, Judy; Godwin, Andrew K; Osorio, Ana; Factor, Rachel E; Terry, Mary B; Rebbeck, Timothy R; Karlan, Beth Y; Southey, Melissa; Rashid, Muhammad; Tung, Nadine; Pharoah, Paul; Blows, Fiona M; Dunning, Alison M; Provenzano, Elena; Hall, Per; Czene, Kamila; Schmidt, Marjanka K; Broeks, Annegien; Cornelissen, Sten; Verhoef, Senno; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Slamon, Dennis J; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Aittomäki, Kristiina; Muranen, Taru A; Heikkilä, Päivi; Blomqvist, Carl; Figueroa, Jonine; Chanock, Stephen J; Brinton, Louise; Lissowska, Jolanta; Olson, Janet E; Pankratz, Vernon S; John, Esther M; Whittemore, Alice S; West, Dee W; Hamann, Ute; Torres, Diana; Ulmer, Hans; Rüdiger, Thomas; Devilee, Peter; Tollenaar, Robert; Seynaeve, Caroline; Van Asperen, Christi J; Eccles, Diana M; Tapper, William J; Durcan, Lorraine; Jones, Louise; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Dwek, Miriam; Swann, Ruth; Bane, Anita L; Glendon, Gord; Mulligan, Anna M; Giles, Graham G; Milne, Roger L; Baglietto, Laura; McLean, Catriona; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Cox, Angela; Cross, Simon S; Reed, Malcolm; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Dörk, Thilo; Bogdanova, Natalia; Park-Simon, Tjoung-Won; Hillemanns, Peter; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Burwinkel, Barbara; Marme, Frederik; Surovy, Harald; Yang, Rongxi; Anton-Culver, Hoda; Ziogas, Argyrios; Hooning, Maartje J; Collée, J; Martens, John; Tilanus-Linthorst, Madeleine; Brenner, Hermann; Dieffenbach, Aida; Arndt, Volke; Stegmaier, Christa; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Lindblom, Annika; Margolin, Sara; Joseph, Vijai; Robson, Mark; Rau-Murthy, Rohini; González-Neira, Anna; Arias, José; Zamora, Pilar; Benítez, Javier; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Peterlongo, Paolo; Zaffaroni, Daniela; Barile, Monica; Capra, Fabio; Radice, Paolo; Teo, Soo H; Easton, Douglas F; Antoniou, Antonis C; Chenevix-Trench, Georgia; Goldgar, David E; ABCTB Investigators.

in: BREAST CANCER RES, Jahrgang 16, Nr. 6, 01.01.2014, S. 3419.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Spurdle, AB, Couch, FJ, Parsons, MT, McGuffog, L, Barrowdale, D, Bolla, MK, Wang, Q, Healey, S, Schmutzler, R, Wappenschmidt, B, Rhiem, K, Hahnen, E, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Ellis, S, Frost, D, Platte, R, Perkins, J, Evans, D, Izatt, L, Eeles, R, Adlard, J, Davidson, R, Cole, T, Scuvera, G, Manoukian, S, Bonanni, B, Mariette, F, Fortuzzi, S, Viel, A, Pasini, B, Papi, L, Varesco, L, Balleine, R, Nathanson, KL, Domchek, SM, Offitt, K, Jakubowska, A, Lindor, N, Thomassen, M, Jensen, U, Rantala, J, Borg, Å, Andrulis, IL, Miron, A, Hansen, T, Caldes, T, Neuhausen, SL, Toland, AE, Nevanlinna, H, Montagna, M, Garber, J, Godwin, AK, Osorio, A, Factor, RE, Terry, MB, Rebbeck, TR, Karlan, BY, Southey, M, Rashid, M, Tung, N, Pharoah, P, Blows, FM, Dunning, AM, Provenzano, E, Hall, P, Czene, K, Schmidt, MK, Broeks, A, Cornelissen, S, Verhoef, S, Fasching, PA, Beckmann, MW, Ekici, AB, Slamon, DJ, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Chang-Claude, J, Flesch-Janys, D, Rudolph, A, Seibold, P, Aittomäki, K, Muranen, TA, Heikkilä, P, Blomqvist, C, Figueroa, J, Chanock, SJ, Brinton, L, Lissowska, J, Olson, JE, Pankratz, VS, John, EM, Whittemore, AS, West, DW, Hamann, U, Torres, D, Ulmer, H, Rüdiger, T, Devilee, P, Tollenaar, R, Seynaeve, C, Van Asperen, CJ, Eccles, DM, Tapper, WJ, Durcan, L, Jones, L, Peto, J, Dos-Santos-Silva, I, Fletcher, O, Johnson, N, Dwek, M, Swann, R, Bane, AL, Glendon, G, Mulligan, AM, Giles, GG, Milne, RL, Baglietto, L, McLean, C, Carpenter, J, Clarke, C, Scott, R, Brauch, H, Brüning, T, Ko, Y-D, Cox, A, Cross, SS, Reed, M, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Gronwald, J, Dörk, T, Bogdanova, N, Park-Simon, T-W, Hillemanns, P, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Burwinkel, B, Marme, F, Surovy, H, Yang, R, Anton-Culver, H, Ziogas, A, Hooning, MJ, Collée, J, Martens, J, Tilanus-Linthorst, M, Brenner, H, Dieffenbach, A, Arndt, V, Stegmaier, C, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Lindblom, A, Margolin, S, Joseph, V, Robson, M, Rau-Murthy, R, González-Neira, A, Arias, J, Zamora, P, Benítez, J, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Peterlongo, P, Zaffaroni, D, Barile, M, Capra, F, Radice, P, Teo, SH, Easton, DF, Antoniou, AC, Chenevix-Trench, G, Goldgar, DE & ABCTB Investigators 2014, 'Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia', BREAST CANCER RES, Jg. 16, Nr. 6, S. 3419. https://doi.org/10.1186/s13058-014-0474-y

APA

Spurdle, A. B., Couch, F. J., Parsons, M. T., McGuffog, L., Barrowdale, D., Bolla, M. K., Wang, Q., Healey, S., Schmutzler, R., Wappenschmidt, B., Rhiem, K., Hahnen, E., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Plendl, H., Niederacher, D., Sutter, C., ... ABCTB Investigators (2014). Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia. BREAST CANCER RES, 16(6), 3419. https://doi.org/10.1186/s13058-014-0474-y

Vancouver

Spurdle AB, Couch FJ, Parsons MT, McGuffog L, Barrowdale D, Bolla MK et al. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia. BREAST CANCER RES. 2014 Jan 1;16(6):3419. https://doi.org/10.1186/s13058-014-0474-y

Bibtex

@article{8b1dd4a3c59348febaed12e861524847,
title = "Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia",
abstract = "INTRODUCTION: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.METHODS: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.RESULTS: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).CONCLUSIONS: These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.",
author = "Spurdle, {Amanda B} and Couch, {Fergus J} and Parsons, {Michael T} and Lesley McGuffog and Daniel Barrowdale and Bolla, {Manjeet K} and Qin Wang and Sue Healey and Rita Schmutzler and Barbara Wappenschmidt and Kerstin Rhiem and Eric Hahnen and Christoph Engel and Alfons Meindl and Nina Ditsch and Norbert Arnold and Hansjoerg Plendl and Dieter Niederacher and Christian Sutter and Shan Wang-Gohrke and Doris Steinemann and Sabine Preisler-Adams and Karin Kast and Raymonda Varon-Mateeva and Steve Ellis and Debra Frost and Radka Platte and Jo Perkins and D Evans and Louise Izatt and Ros Eeles and Julian Adlard and Rosemarie Davidson and Trevor Cole and Giulietta Scuvera and Siranoush Manoukian and Bernardo Bonanni and Frederique Mariette and Stefano Fortuzzi and Alessandra Viel and Barbara Pasini and Laura Papi and Liliana Varesco and Rosemary Balleine and Nathanson, {Katherine L} and Domchek, {Susan M} and Kenneth Offitt and Anna Jakubowska and Noralane Lindor and Mads Thomassen and Uffe Jensen and Johanna Rantala and {\AA}ke Borg and Andrulis, {Irene L} and Alexander Miron and Thomas Hansen and Trinidad Caldes and Neuhausen, {Susan L} and Toland, {Amanda E} and Heli Nevanlinna and Marco Montagna and Judy Garber and Godwin, {Andrew K} and Ana Osorio and Factor, {Rachel E} and Terry, {Mary B} and Rebbeck, {Timothy R} and Karlan, {Beth Y} and Melissa Southey and Muhammad Rashid and Nadine Tung and Paul Pharoah and Blows, {Fiona M} and Dunning, {Alison M} and Elena Provenzano and Per Hall and Kamila Czene and Schmidt, {Marjanka K} and Annegien Broeks and Sten Cornelissen and Senno Verhoef and Fasching, {Peter A} and Beckmann, {Matthias W} and Ekici, {Arif B} and Slamon, {Dennis J} and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G} and Nielsen, {Sune F} and Henrik Flyger and Jenny Chang-Claude and Dieter Flesch-Janys and Anja Rudolph and Petra Seibold and Kristiina Aittom{\"a}ki and Muranen, {Taru A} and P{\"a}ivi Heikkil{\"a} and Carl Blomqvist and Jonine Figueroa and Chanock, {Stephen J} and Louise Brinton and Jolanta Lissowska and Olson, {Janet E} and Pankratz, {Vernon S} and John, {Esther M} and Whittemore, {Alice S} and West, {Dee W} and Ute Hamann and Diana Torres and Hans Ulmer and Thomas R{\"u}diger and Peter Devilee and Robert Tollenaar and Caroline Seynaeve and {Van Asperen}, {Christi J} and Eccles, {Diana M} and Tapper, {William J} and Lorraine Durcan and Louise Jones and Julian Peto and Isabel Dos-Santos-Silva and Olivia Fletcher and Nichola Johnson and Miriam Dwek and Ruth Swann and Bane, {Anita L} and Gord Glendon and Mulligan, {Anna M} and Giles, {Graham G} and Milne, {Roger L} and Laura Baglietto and Catriona McLean and Jane Carpenter and Christine Clarke and Rodney Scott and Hiltrud Brauch and Thomas Br{\"u}ning and Yon-Dschun Ko and Angela Cox and Cross, {Simon S} and Malcolm Reed and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Jacek Gronwald and Thilo D{\"o}rk and Natalia Bogdanova and Tjoung-Won Park-Simon and Peter Hillemanns and Haiman, {Christopher A} and Henderson, {Brian E} and Fredrick Schumacher and {Le Marchand}, Loic and Barbara Burwinkel and Frederik Marme and Harald Surovy and Rongxi Yang and Hoda Anton-Culver and Argyrios Ziogas and Hooning, {Maartje J} and J Coll{\'e}e and John Martens and Madeleine Tilanus-Linthorst and Hermann Brenner and Aida Dieffenbach and Volke Arndt and Christa Stegmaier and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Annika Lindblom and Sara Margolin and Vijai Joseph and Mark Robson and Rohini Rau-Murthy and Anna Gonz{\'a}lez-Neira and Jos{\'e} Arias and Pilar Zamora and Javier Ben{\'i}tez and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Hartikainen, {Jaana M} and Paolo Peterlongo and Daniela Zaffaroni and Monica Barile and Fabio Capra and Paolo Radice and Teo, {Soo H} and Easton, {Douglas F} and Antoniou, {Antonis C} and Georgia Chenevix-Trench and Goldgar, {David E} and {ABCTB Investigators}",
year = "2014",
month = jan,
day = "1",
doi = "10.1186/s13058-014-0474-y",
language = "English",
volume = "16",
pages = "3419",
journal = "BREAST CANCER RES",
issn = "1465-5411",
publisher = "BioMed Central Ltd.",
number = "6",

}

RIS

TY - JOUR

T1 - Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

AU - Spurdle, Amanda B

AU - Couch, Fergus J

AU - Parsons, Michael T

AU - McGuffog, Lesley

AU - Barrowdale, Daniel

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Healey, Sue

AU - Schmutzler, Rita

AU - Wappenschmidt, Barbara

AU - Rhiem, Kerstin

AU - Hahnen, Eric

AU - Engel, Christoph

AU - Meindl, Alfons

AU - Ditsch, Nina

AU - Arnold, Norbert

AU - Plendl, Hansjoerg

AU - Niederacher, Dieter

AU - Sutter, Christian

AU - Wang-Gohrke, Shan

AU - Steinemann, Doris

AU - Preisler-Adams, Sabine

AU - Kast, Karin

AU - Varon-Mateeva, Raymonda

AU - Ellis, Steve

AU - Frost, Debra

AU - Platte, Radka

AU - Perkins, Jo

AU - Evans, D

AU - Izatt, Louise

AU - Eeles, Ros

AU - Adlard, Julian

AU - Davidson, Rosemarie

AU - Cole, Trevor

AU - Scuvera, Giulietta

AU - Manoukian, Siranoush

AU - Bonanni, Bernardo

AU - Mariette, Frederique

AU - Fortuzzi, Stefano

AU - Viel, Alessandra

AU - Pasini, Barbara

AU - Papi, Laura

AU - Varesco, Liliana

AU - Balleine, Rosemary

AU - Nathanson, Katherine L

AU - Domchek, Susan M

AU - Offitt, Kenneth

AU - Jakubowska, Anna

AU - Lindor, Noralane

AU - Thomassen, Mads

AU - Jensen, Uffe

AU - Rantala, Johanna

AU - Borg, Åke

AU - Andrulis, Irene L

AU - Miron, Alexander

AU - Hansen, Thomas

AU - Caldes, Trinidad

AU - Neuhausen, Susan L

AU - Toland, Amanda E

AU - Nevanlinna, Heli

AU - Montagna, Marco

AU - Garber, Judy

AU - Godwin, Andrew K

AU - Osorio, Ana

AU - Factor, Rachel E

AU - Terry, Mary B

AU - Rebbeck, Timothy R

AU - Karlan, Beth Y

AU - Southey, Melissa

AU - Rashid, Muhammad

AU - Tung, Nadine

AU - Pharoah, Paul

AU - Blows, Fiona M

AU - Dunning, Alison M

AU - Provenzano, Elena

AU - Hall, Per

AU - Czene, Kamila

AU - Schmidt, Marjanka K

AU - Broeks, Annegien

AU - Cornelissen, Sten

AU - Verhoef, Senno

AU - Fasching, Peter A

AU - Beckmann, Matthias W

AU - Ekici, Arif B

AU - Slamon, Dennis J

AU - Bojesen, Stig E

AU - Nordestgaard, Børge G

AU - Nielsen, Sune F

AU - Flyger, Henrik

AU - Chang-Claude, Jenny

AU - Flesch-Janys, Dieter

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Aittomäki, Kristiina

AU - Muranen, Taru A

AU - Heikkilä, Päivi

AU - Blomqvist, Carl

AU - Figueroa, Jonine

AU - Chanock, Stephen J

AU - Brinton, Louise

AU - Lissowska, Jolanta

AU - Olson, Janet E

AU - Pankratz, Vernon S

AU - John, Esther M

AU - Whittemore, Alice S

AU - West, Dee W

AU - Hamann, Ute

AU - Torres, Diana

AU - Ulmer, Hans

AU - Rüdiger, Thomas

AU - Devilee, Peter

AU - Tollenaar, Robert

AU - Seynaeve, Caroline

AU - Van Asperen, Christi J

AU - Eccles, Diana M

AU - Tapper, William J

AU - Durcan, Lorraine

AU - Jones, Louise

AU - Peto, Julian

AU - Dos-Santos-Silva, Isabel

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Dwek, Miriam

AU - Swann, Ruth

AU - Bane, Anita L

AU - Glendon, Gord

AU - Mulligan, Anna M

AU - Giles, Graham G

AU - Milne, Roger L

AU - Baglietto, Laura

AU - McLean, Catriona

AU - Carpenter, Jane

AU - Clarke, Christine

AU - Scott, Rodney

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Ko, Yon-Dschun

AU - Cox, Angela

AU - Cross, Simon S

AU - Reed, Malcolm

AU - Lubinski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katarzyna

AU - Gronwald, Jacek

AU - Dörk, Thilo

AU - Bogdanova, Natalia

AU - Park-Simon, Tjoung-Won

AU - Hillemanns, Peter

AU - Haiman, Christopher A

AU - Henderson, Brian E

AU - Schumacher, Fredrick

AU - Le Marchand, Loic

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Surovy, Harald

AU - Yang, Rongxi

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Hooning, Maartje J

AU - Collée, J

AU - Martens, John

AU - Tilanus-Linthorst, Madeleine

AU - Brenner, Hermann

AU - Dieffenbach, Aida

AU - Arndt, Volke

AU - Stegmaier, Christa

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Joseph, Vijai

AU - Robson, Mark

AU - Rau-Murthy, Rohini

AU - González-Neira, Anna

AU - Arias, José

AU - Zamora, Pilar

AU - Benítez, Javier

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli-Matti

AU - Hartikainen, Jaana M

AU - Peterlongo, Paolo

AU - Zaffaroni, Daniela

AU - Barile, Monica

AU - Capra, Fabio

AU - Radice, Paolo

AU - Teo, Soo H

AU - Easton, Douglas F

AU - Antoniou, Antonis C

AU - Chenevix-Trench, Georgia

AU - Goldgar, David E

AU - ABCTB Investigators

PY - 2014/1/1

Y1 - 2014/1/1

N2 - INTRODUCTION: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.METHODS: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.RESULTS: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).CONCLUSIONS: These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.

AB - INTRODUCTION: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.METHODS: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.RESULTS: ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).CONCLUSIONS: These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.

U2 - 10.1186/s13058-014-0474-y

DO - 10.1186/s13058-014-0474-y

M3 - SCORING: Journal article

C2 - 25857409

VL - 16

SP - 3419

JO - BREAST CANCER RES

JF - BREAST CANCER RES

SN - 1465-5411

IS - 6

ER -