The University of Southampton
University of Southampton Institutional Repository

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

Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA)
Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA)
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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Wang, X.
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Fredericksen, Z.
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Lindor, N.M.
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Szabo, C.
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Gaudet, M.M.
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Singer, C.F.
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Tea, M.-K.
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Greene, M.H.
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Sokolenko, A.
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Imyanitov, E.
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Mavaddat, N., Barrowdale, D. and Andrulis, I.L. et al. (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. (doi:10.1158/1055-9965.EPI-11-0775).

Record type: Article

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.

Full text not available from this repository.

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Published date: January 2012
Organisations: Cancer Sciences

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Local EPrints ID: 352342
URI: https://eprints.soton.ac.uk/id/eprint/352342
PURE UUID: 5115a2e3-6cef-4aac-acdc-5dd3311aacff

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Date deposited: 13 May 2013 10:30
Last modified: 16 Jul 2019 21:34

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Contributors

Author: N. Mavaddat
Author: D. Barrowdale
Author: I.L. Andrulis
Author: S.M. Domchek
Author: D. Eccles
Author: H. Nevanlinna
Author: S.J. Ramus
Author: A. Spurdle
Author: M. Robson
Author: M. Sherman
Author: A.M. Mulligan
Author: F.J. Couch
Author: C. Engel
Author: L. McGuffog
Author: S. Healey
Author: O.M. Sinilnikova
Author: M.C. Southey
Author: M.B. Terry
Author: D. Goldgar
Author: F. O'Malley
Author: E. M. John
Author: R. Janavicius
Author: L. Tihomirova
Author: T.V.O. Hansen
Author: F.C. Nielsen
Author: A. Osorio
Author: A. Stavropoulou
Author: J. Benitez
Author: S. Manoukian
Author: B. Peissel
Author: M. Barile
Author: S. Volorio
Author: B. Pasini
Author: R. Dolcetti
Author: A.L. Putignano
Author: L. Ottini
Author: P. Radice
Author: U. Hamann
Author: M.U. Rashid
Author: F.B. Hogervorst
Author: M. Kriege
Author: R.B. van der Luijt
Author: S. Peock
Author: D. Frost
Author: D.G. Evans
Author: C. Brewer
Author: L. Walker
Author: M.T. Rogers
Author: L.E. Side
Author: C. Houghton
Author: J. Weaver
Author: A.K. Godwin
Author: R.K. Schmutzler
Author: B. Wappenschmidt
Author: A. Meindl
Author: K. Kast
Author: N. Arnold
Author: D. Niederacher
Author: C. Sutter
Author: H. Deissler
Author: D. Gadzicki
Author: S. Preisler-Adams
Author: R. Varon-Mateeva
Author: I. Schonbuchner
Author: H. Gevensleben
Author: D. Stoppa-Lyonnet
Author: M. Belotti
Author: L. Barjhoux
Author: C. Isaacs
Author: B.N. Peshkin
Author: T. Caldes
Author: M. de la Hoya
Author: C. Canadas
Author: T. Heikkinen
Author: P. Heikkila
Author: K. Aittomaki
Author: I. Blanco
Author: C. Lazaro
Author: J. Brunet
Author: B.A. Agnarsson
Author: A. Arason
Author: R.B. Barkardottir
Author: M. Dumont
Author: J. Simard
Author: M. Montagna
Author: S. Agata
Author: E. D'Andrea
Author: M. Yan
Author: S. Fox
Author: T.R. Rebbeck
Author: W. Rubinstein
Author: N. Tung
Author: J.E. Garber
Author: X. Wang
Author: Z. Fredericksen
Author: V.S. Pankratz
Author: N.M. Lindor
Author: C. Szabo
Author: K. Offit
Author: R. Sakr
Author: M.M. Gaudet
Author: C.F. Singer
Author: M.-K. Tea
Author: C. Rappaport
Author: P. L. Mai
Author: M.H. Greene
Author: A. Sokolenko
Author: E. Imyanitov
Author: A.E. Toland
Author: L. Senter
Author: K. Sweet
Author: M. Thomassen
Author: A.-M. Gerdes
Author: T. Kruse
Author: M. Caligo
Author: P. Aretini
Author: J. Rantala
Author: A. von Wachenfeld
Author: K. Henriksson
Author: L. Steele
Author: S.L. Neuhausen
Author: R. Nussbaum
Author: M. Beattie
Author: K. Odunsi
Author: L. Sucheston
Author: S.A. Gayther
Author: K. Nathanson
Author: J. Gross
Author: C. Walsh
Author: B. Karlan
Author: G. Chenevix-Trench
Author: D.F. Easton
Author: A.C. Antoniou

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