PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants.
About this Publication
Title
PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants.
Pubmed ID
37173335
(View this publication on the PubMed website)
Digital Object Identifier
Publication
NPJ Breast Cancer. 2023 May 12; Volume 9 (Issue 1): Pages 37
Authors
Muranen TA, Morra A, Khan S, Barnes DR, Bolla MK, Dennis J, Keeman R, Leslie G, Parsons MT, Wang Q, Ahearn TU, Aittomäki K, Andrulis IL, Arun BK, Behrens S, Bialkowska K, Bojesen SE, Camp NJ, Chang-Claude J, Czene K, ...show more Devilee P, HEBON investigators, Domchek SM, Dunning AM, Engel C, Evans DG, Gago-Dominguez M, García-Closas M, Gerdes AM, Glendon G, Guénel P, Hahnen E, Hamann U, Hanson H, Hooning MJ, Hoppe R, Izatt L, Jakubowska A, James PA, Kristensen VN, Lalloo F, Lindeman GJ, Mannermaa A, Margolin S, Neuhausen SL, Newman WG, Peterlongo P, Phillips KA, Pujana MA, Rantala J, Rønlund K, Saloustros E, Schmutzler RK, Schneeweiss A, Singer CF, Suvanto M, Tan YY, Teixeira MR, Thomassen M, Tischkowitz M, Tripathi V, Wappenschmidt B, Zhao E, Easton DF, Antoniou AC, Chenevix-Trench G, Pharoah PDP, Schmidt MK, Blomqvist C, Nevanlinna H
Affiliations
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. taru.a.muranen@helsinki.fi.
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
- Population Health Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
- Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
- Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
- Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
- Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
- Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
- Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
- Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University Hospital Foundation NHS Trust, Manchester, UK.
- Health Research Institute of Santiago de Compostela Foundation (FIDIS), SERGAS, Cancer Genetics and Epidemiology Group Santiago de Compostela, Santiago de Compostela, Spain.
- Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
- Team "Exposome and Heredity", CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ, Villejuif, France.
- Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- SouthWest Thames Centre for Genomics, St George's University Hospital's NHS Foundation Trust, London, UK.
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
- Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
- Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
- Clinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals Foundation Trust, Manchester, UK.
- Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
- Department of Oncology, Stockholm South General Hospital (Södersjukhuset), Stockholm, Sweden.
- Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
- Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
- Genome Diagnostics Program, IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy.
- Department of Medical Oncology, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
- Translational Research Laboratory, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC, Barcelona, Spain.
- Clinical Genetics, Karolinska Institutet, Stockholm, Sweden.
- Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle Hospital, Vejle, Denmark.
- Department of Oncology, University Hospital of Larissa, Larissa, Greece.
- National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany.
- Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
- Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
- Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark.
- Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
- Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
- Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Abstract
We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but the confidence intervals always included the calibration slope. Altogether, our results encourage the use of the PREDICT ER-negative model in management of breast cancer patients with germline BRCA1 variants. For the PREDICT ER-positive model, the discrimination was slightly lower in BRCA2 variant carriers (concordance 0.60 in CIMBA, 0.65 in BCAC). Especially, inclusion of the tumor grade distorted the prognostic estimates. The breast cancer mortality of BRCA2 carriers was underestimated at the low end of the PREDICT score distribution, whereas at the high end, the mortality was overestimated. These data suggest that BRCA2 status should also be taken into consideration with tumor characteristics, when estimating the prognosis of ER-positive breast cancer patients.
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