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 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'Malley; Esther 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; Anne-Marie Gerdes; for HEBON

doi:10.1158/1055-9965.EPI-11-0775

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 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, Anne-Marie Gerdes, for HEBON

338 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 language	English
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	21
Issue number	1
Pages (from-to)	134-147
Number of pages	14
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.EPI-11-0775
Publication status	Published - Jan 2012

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10.1158/1055-9965.EPI-11-0775

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Mavaddat, N., Barrowdale, D., Andrulis, I. L., Domchek, S. M., Eccles, D., Nevanlinna, H., Ramus, S. J., Spurdle, A., Robson, M., Sherman, M., Mulligan, A. M., Couch, F. J., Engel, C., McGuffog, L., Healey, S., Sinilnikova, O. M., Southey, M. C., Terry, M. B., Goldgar, D., ... for HEBON (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 & Prevention, 21(1), 134-147. https://doi.org/10.1158/1055-9965.EPI-11-0775

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 et al.

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

Research output: Contribution to journal › Journal article › Research › peer-review

Mavaddat, N, Barrowdale, D, Andrulis, IL, Domchek, SM, Eccles, D, Nevanlinna, H, Ramus, SJ, Spurdle, A, Robson, M, Sherman, M, 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, Gerdes, A-M & for HEBON 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 & Prevention, vol. 21, no. 1, pp. 134-147. https://doi.org/10.1158/1055-9965.EPI-11-0775

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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 Mark Sherman 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 Anne-Marie Gerdes and Nielsen, {Finn Cilius}",

year = "2012",

month = jan,

doi = "10.1158/1055-9965.EPI-11-0775",

language = "English",

volume = "21",

pages = "134--147",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

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TY - JOUR

T1 - Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: 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

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 - Gerdes, Anne-Marie

AU - for HEBON

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.

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

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

M3 - Journal article

C2 - 22144499

SN - 1055-9965

VL - 21

SP - 134

EP - 147

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 1

ER -

Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

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