Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

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)

HEBON

War Studies

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, University of Cambridge, Cambridge, United Kingdom.

Research output: Contribution to journal › Article › peer-review

521 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
Pages (from-to)	134-47
Number of pages	14
Journal	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume	21
Issue number	1
DOIs	https://doi.org/10.1158/1055-9965.EPI-11-0775
Publication status	Published - Jan 2012

Keywords

Adult
Aged
Breast Neoplasms/genetics
Female
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Middle Aged
Neoplasm Grading
Ovarian Neoplasms/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1158/1055-9965.EPI-11-0775

Cite this

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 : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 21(1), 134-47. https://doi.org/10.1158/1055-9965.EPI-11-0775

HEBON. / 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 & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012 ; Vol. 21, No. 1. pp. 134-47.

@article{838777794be84a3c81d3100f0785caa4,

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.",

keywords = "Adult, Aged, Breast Neoplasms/genetics, Female, Genes, BRCA1, Genes, BRCA2, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Middle Aged, Neoplasm Grading, Ovarian Neoplasms/genetics",

author = "HEBON and 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 Catherine Houghton",

year = "2012",

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

language = "English",

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pages = "134--47",

journal = "Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology",

issn = "1055-9965",

publisher = "American Association for Cancer Research",

number = "1",

}

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 : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 21, no. 1, pp. 134-47. 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). / HEBON.
In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Vol. 21, No. 1, 01.2012, p. 134-47.

Research output: Contribution to journal › Article › peer-review

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 - HEBON

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 - Houghton, Catherine

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.

KW - Adult

KW - Aged

KW - Breast Neoplasms/genetics

KW - Female

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Genetic Predisposition to Disease

KW - Germ-Line Mutation

KW - Humans

KW - Middle Aged

KW - Neoplasm Grading

KW - Ovarian Neoplasms/genetics

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

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

M3 - Article

C2 - 22144499

SN - 1055-9965

VL - 21

SP - 134

EP - 147

JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

IS - 1

ER -

HEBON. 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 : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012 Jan;21(1):134-47. 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)

Abstract

Keywords

UN SDGs

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