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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Spurdle AB, Couch FJ, Parsons MT, Mcguffog L, Barrowdale D, Bolla MK, Wang Q, Healey S, Schmutzler RK, 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 DG, 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 UB, Rantala J, Borg A, Andrulis IL, Miron A, Hansen TVO, 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 MU, Tung N, Pharoah PDP, Blows FM, Dunning AM, Provenzano E, Hall P, Czene K, Schmidt MK, Broeks A, Cornelissen S, Verhoef S, Fasching PA, Beckmann M, Ekici AB, Slamon DJ, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Chang-Claude J, Flesch-Janys D, Rudolph A, Seibold P, Aittomaki K, Muranen TA, Heikkila 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 HU, Rudiger T, Devilee P, Tollenaar RAEM, 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, Bruning T, Ko YD, Cox A, Cross SS, Reed MWR, Lubinski J, Jaworska-Bieniek K, Durda K, Gronwald J, Dork T, Bogdanova N, Park-Simon TW, 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, Collee JM, Martens JWM, Tilanus-Linthorst MMA, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Lindblom A, Margolin S, Joseph V, Robson M, Rau-Murthy R, Gonzalez-Neira A, Arias JI, Zamora P, Benitez J, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Peterlongo P, Zaffaroni D, Barile M, Capra F, Radice P, Teo SH, Easton DF, Antoniou AC, Chenevix-Trench G, Goldgar DE
Zeitschrift: Breast Cancer Research
Verlag: BioMed Central
Jahr der Veröffentlichung: 2014
Band: 16
Heftnummer: 6
Seitenbereich: 3419
ISSN: 1465-542X


Abstract


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.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.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)).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.



FAU-Autoren / FAU-Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut


Autor(en) der externen Einrichtung(en)
Aarhus University Hospital / Aarhus Universitetshospital
Antoni van Leeuwenhoek
Birmingham Women's NHS Foundation Trust
Cancer Council Victoria
Cancer Prevention Institute of California (CPIC)
Case Western Reserve University
Cedars-Sinai Medical Center
Central Manchester University Hospitals
Centro di Riferimento Oncologico (CRO)
Chapel Allerton Hospital
Charité - Universitätsmedizin Berlin
Christian-Albrechts-Universität zu Kiel
City of Hope Medical Center
Columbia University
Copenhagen University Hospital
Dana–Farber Cancer Institute
Deutsches Krebsforschungszentrum (DKFZ)
Eberhard Karls Universität Tübingen
Erasmus University Medical Center
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Evangelische Kliniken Bonn gGmbH
Fondazione IRCCS: Istituto Nazionale dei Tumori
Guy's and St Thomas'
Hamilton Health Sciences (HHS)
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Heinrich-Heine-Universität Düsseldorf
Helsingin yliopisto / University of Helsinki
Hospital Clínico San Carlos
Hospital Monte Naranco
Hospital Universitario La Paz
IFOM - FIRC Institute of Molecular Oncology
Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA)
Istituto Oncologico Veneto (IOV), IRCCS
Karolinska Institute
Karolinska University Hospital / Karolinska Universitetssjukhuset
Klinikum Mittelbaden Baden-Baden Balg
Krebsregister Saarland / Saarland Cancer Registry
Leiden University
London School of Hygiene and Tropical Medicine
Ludwig-Maximilians-Universität (LMU)
Lund University / Lunds universitet
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Memorial Sloan Kettering Cancer Center
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
Odense Universitetshospital (OUH)
Ohio State University
Ospedale San Martino (IRCCS AOU)
Oulun Yliopisto / University of Oulo
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Queen Mary, University of London
Ramsay Sime Darby Health Care (RSDHC)
Ruprecht-Karls-Universität Heidelberg
Southern General Hospital
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Städtisches Klinikum Karlsruhe
Stanford University
Technische Universität Dresden
Technische Universität München (TUM)
The Alfred Hospital
The University of Melbourne
Università degli Studi di Firenze / University of Florence
Universität Köln
Universität Leipzig
Universitätsklinikum Hamburg-Eppendorf (UKE)
Universitätsklinikum Heidelberg
Universitätsklinikum Ulm
University Health Network (UHN)
University of California Irvine
University of California Los Angeles (UCLA)
University of Cambridge
University of Eastern Finland
University of Hawaii (U.H.)
University of Kansas (KU)
University of Newcastle (UoN)
University of Pennsylvania
University of Sheffield
University of Southampton
University of Southern California (USC)
University of Sydney
University of Toronto
University of Turin / Università degli Studi di Torino (UNITO)
University of Utah
University of Westminster
Westfälische Wilhelms-Universität (WWU) Münster


Zitierweisen

APA:
Spurdle, A.B., Couch, F.J., Parsons, M.T., Mcguffog, L., Barrowdale, D., Bolla, M.K.,... Goldgar, D.E. (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 Research, 16(6), 3419. https://dx.doi.org/10.1186/s13058-014-0474-y

MLA:
Spurdle, Amanda B., 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 Research 16.6 (2014): 3419.

BibTeX: 

Zuletzt aktualisiert 2018-08-10 um 08:27