Morphological predictors of BRCA1 germline mutations in young women with breast cancer
Identifieur interne : 006431 ( Main/Merge ); précédent : 006430; suivant : 006432Morphological predictors of BRCA1 germline mutations in young women with breast cancer
Auteurs : M C Southey [Australie] ; S J Ramus [Royaume-Uni] ; J G Dowty [Australie] ; L D Smith [Australie] ; A A Tesoriero [Australie] ; E E M. Wong [Australie] ; G S Dite [Australie] ; M A Jenkins [Australie] ; G B Byrnes [France] ; I. Winship [Australie] ; K-A Phillips [Australie] ; G G Giles [Australie] ; J L Hopper [Australie]Source :
- British Journal of Cancer [ 0007-0920 ] ; 2011.
Abstract
Knowing a young woman with newly diagnosed breast cancer has a germline
We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a
The probability of being a
Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost all
Url:
DOI: 10.1038/bjc.2011.41
PubMed: 21343941
PubMed Central: 3065278
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Morphological predictors of <italic>BRCA1</italic> germline mutations in young women with breast cancer</title><author><name sortKey="Southey, M C" sort="Southey, M C" uniqKey="Southey M" first="M C" last="Southey">M C Southey</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Ramus, S J" sort="Ramus, S J" uniqKey="Ramus S" first="S J" last="Ramus">S J Ramus</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Gynaecological Oncology, UCL EGA Institute for Women's Health, University College London</institution>, London,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dowty, J G" sort="Dowty, J G" uniqKey="Dowty J" first="J G" last="Dowty">J G Dowty</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Smith, L D" sort="Smith, L D" uniqKey="Smith L" first="L D" last="Smith">L D Smith</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Tesoriero, A A" sort="Tesoriero, A A" uniqKey="Tesoriero A" first="A A" last="Tesoriero">A A Tesoriero</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Wong, E E M" sort="Wong, E E M" uniqKey="Wong E" first="E E M" last="Wong">E E M. Wong</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Dite, G S" sort="Dite, G S" uniqKey="Dite G" first="G S" last="Dite">G S Dite</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jenkins, M A" sort="Jenkins, M A" uniqKey="Jenkins M" first="M A" last="Jenkins">M A Jenkins</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Byrnes, G B" sort="Byrnes, G B" uniqKey="Byrnes G" first="G B" last="Byrnes">G B Byrnes</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>The International Agency for Research on Cancer</institution>, Lyon,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Winship, I" sort="Winship, I" uniqKey="Winship I" first="I" last="Winship">I. Winship</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Medicine (Royal Melbourne Hospital), The University of Melbourne</institution>, Parkville, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Genetics, Royal Melbourne Hospital</institution>, Parkville, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Phillips, K A" sort="Phillips, K A" uniqKey="Phillips K" first="K-A" last="Phillips">K-A Phillips</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre</institution>, Victoria,<country>East Melbourne, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Department of Medicine, St Vincent's Hospital</institution>, Victoria,<country>East Melbourne, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Giles, G G" sort="Giles, G G" uniqKey="Giles G" first="G G" last="Giles">G G Giles</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>Cancer Epidemiology Centre, The Cancer Council Victoria</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Hopper, J L" sort="Hopper, J L" uniqKey="Hopper J" first="J L" last="Hopper">J L Hopper</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21343941</idno><idno type="pmc">3065278</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065278</idno><idno type="RBID">PMC:3065278</idno><idno type="doi">10.1038/bjc.2011.41</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000089</idno><idno 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wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Ramus, S J" sort="Ramus, S J" uniqKey="Ramus S" first="S J" last="Ramus">S J Ramus</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Gynaecological Oncology, UCL EGA Institute for Women's Health, University College London</institution>, London,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dowty, J G" sort="Dowty, J G" uniqKey="Dowty J" first="J G" last="Dowty">J G Dowty</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Smith, L D" sort="Smith, L D" uniqKey="Smith L" first="L D" last="Smith">L D Smith</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Tesoriero, A A" sort="Tesoriero, A A" uniqKey="Tesoriero A" first="A A" last="Tesoriero">A A Tesoriero</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Wong, E E M" sort="Wong, E E M" uniqKey="Wong E" first="E E M" last="Wong">E E M. Wong</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Dite, G S" sort="Dite, G S" uniqKey="Dite G" first="G S" last="Dite">G S Dite</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jenkins, M A" sort="Jenkins, M A" uniqKey="Jenkins M" first="M A" last="Jenkins">M A Jenkins</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Byrnes, G B" sort="Byrnes, G B" uniqKey="Byrnes G" first="G B" last="Byrnes">G B Byrnes</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>The International Agency for Research on Cancer</institution>, Lyon,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Winship, I" sort="Winship, I" uniqKey="Winship I" first="I" last="Winship">I. Winship</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Medicine (Royal Melbourne Hospital), The University of Melbourne</institution>, Parkville, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Genetics, Royal Melbourne Hospital</institution>, Parkville, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Phillips, K A" sort="Phillips, K A" uniqKey="Phillips K" first="K-A" last="Phillips">K-A Phillips</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre</institution>, Victoria,<country>East Melbourne, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Department of Medicine, St Vincent's Hospital</institution>, Victoria,<country>East Melbourne, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Giles, G G" sort="Giles, G G" uniqKey="Giles G" first="G G" last="Giles">G G Giles</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Pathology, Genetic Epidemiology Laboratory</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>Cancer Epidemiology Centre, The Cancer Council Victoria</institution>, Victoria,<country>Carlton, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea></wicri:regionArea></affiliation></author><author><name sortKey="Hopper, J L" sort="Hopper, J L" uniqKey="Hopper J" first="J L" last="Hopper">J L Hopper</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Public Health, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne</institution>, Carlton, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">British Journal of Cancer</title><idno type="ISSN">0007-0920</idno><idno type="eISSN">1532-1827</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background:</title><p>Knowing a young woman with newly diagnosed breast cancer has a germline <italic>BRCA1</italic> mutation informs her clinical management and that of her relatives. We sought an optimal strategy for identifying carriers using family history, breast cancer morphology and hormone receptor status data.</p></sec><sec><title>Methods:</title><p>We studied a population-based sample of 452 Australian women with invasive breast cancer diagnosed before age 40 years for whom we conducted extensive germline mutation testing (29 carried a <italic>BRCA1</italic> mutation) and a systematic pathology review, and collected three-generational family history and tumour ER and PR status. Predictors of mutation status were identified using multiple logistic regression. Areas under receiver operator characteristic (ROC) curves were estimated using five-fold stratified cross-validation.</p></sec><sec><title>Results:</title><p>The probability of being a <italic>BRCA1</italic> mutation carrier increased with number of selected histology features even after adjusting for family history and ER and PR status (<italic>P</italic><0.0001). From the most parsimonious multivariate model, the odds ratio for being a carrier were: 9.7 (95% confidence interval: 2.6–47.0) for trabecular growth pattern (<italic>P</italic>=0.001); 7.8 (2.7–25.7) for mitotic index over 50 mitoses per 10 high-powered field (<italic>P</italic>=0.0003); and 2.7 (1.3–5.9) for each first-degree relative with breast cancer diagnosed before age 60 years (<italic>P</italic>=0.01).The area under the ROC curve was 0.87 (0.83–0.90).</p></sec><sec><title>Conclusion:</title><p>Pathology review, with attention to a few specific morphological features of invasive breast cancers, can identify almost all <italic>BRCA1</italic> germline mutation carriers among women with early-onset breast cancer without taking into account family history.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Antoniou, Ac" uniqKey="Antoniou A">AC Antoniou</name></author><author><name sortKey="Cunningham, Ap" uniqKey="Cunningham A">AP Cunningham</name></author><author><name sortKey="Peto, J" uniqKey="Peto J">J Peto</name></author><author><name sortKey="Evans, Dg" uniqKey="Evans D">DG Evans</name></author><author><name sortKey="Lalloo, F" uniqKey="Lalloo F">F Lalloo</name></author><author><name sortKey="Narod, Sa" uniqKey="Narod S">SA Narod</name></author><author><name sortKey="Risch, Ha" uniqKey="Risch H">HA Risch</name></author><author><name sortKey="Eyfjord, Je" uniqKey="Eyfjord J">JE Eyfjord</name></author><author><name sortKey="Hopper, Jl" uniqKey="Hopper J">JL Hopper</name></author><author><name sortKey="Southey, Mc" uniqKey="Southey M">MC Southey</name></author><author><name sortKey="Olsson, H" uniqKey="Olsson H">H Olsson</name></author><author><name sortKey="Johannsson, O" uniqKey="Johannsson O">O Johannsson</name></author><author><name sortKey="Borg, A" uniqKey="Borg A">A Borg</name></author><author><name sortKey="Pasini, B" uniqKey="Pasini B">B Pasini</name></author><author><name 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Shanley</name></author><author><name sortKey="Pichert, G" uniqKey="Pichert G">G Pichert</name></author><author><name sortKey="Izatt, L" uniqKey="Izatt L">L Izatt</name></author><author><name sortKey="Rose, S" uniqKey="Rose S">S Rose</name></author><author><name sortKey="Douglas, F" uniqKey="Douglas F">F Douglas</name></author><author><name sortKey="Eccles, D" uniqKey="Eccles D">D Eccles</name></author><author><name sortKey="Morrison, Pj" uniqKey="Morrison P">PJ Morrison</name></author><author><name sortKey="Scott, J" uniqKey="Scott J">J Scott</name></author><author><name sortKey="Zimmern, Rl" uniqKey="Zimmern R">RL Zimmern</name></author><author><name sortKey="Easton, Df" uniqKey="Easton D">DF Easton</name></author><author><name sortKey="Pharoah, Pd" uniqKey="Pharoah P">PD Pharoah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antoniou, A" uniqKey="Antoniou A">A Antoniou</name></author><author><name sortKey="Pharoah, Pd" uniqKey="Pharoah P">PD 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sortKey="Whitty, J" uniqKey="Whitty J">J Whitty</name></author><author><name sortKey="Grubb, G" uniqKey="Grubb G">G Grubb</name></author><author><name sortKey="St John, Djb" uniqKey="St John D">DJB St John</name></author><author><name sortKey="Macrae, F" uniqKey="Macrae F">F Macrae</name></author><author><name sortKey="Young, J" uniqKey="Young J">J Young</name></author><author><name sortKey="Barker, M" uniqKey="Barker M">M Barker</name></author><author><name sortKey="Walsh, M" uniqKey="Walsh M">M Walsh</name></author><author><name sortKey="Royce, Sg" uniqKey="Royce S">SG Royce</name></author><author><name sortKey="Jass, J" uniqKey="Jass J">J Jass</name></author><author><name sortKey="Giles, Gg" uniqKey="Giles G">GG Giles</name></author><author><name sortKey="Hopper, Jl" uniqKey="Hopper J">JL Hopper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vasen, Hf" uniqKey="Vasen H">HF Vasen</name></author><author><name sortKey="Watson, P" uniqKey="Watson 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