npj Breast Cancer (May 2023)
PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants
- Taru A. Muranen,
- Anna Morra,
- Sofia Khan,
- Daniel R. Barnes,
- Manjeet K. Bolla,
- Joe Dennis,
- Renske Keeman,
- Goska Leslie,
- Michael T. Parsons,
- Qin Wang,
- Thomas U. Ahearn,
- Kristiina Aittomäki,
- Irene L. Andrulis,
- Banu K. Arun,
- Sabine Behrens,
- Katarzyna Bialkowska,
- Stig E. Bojesen,
- Nicola J. Camp,
- Jenny Chang-Claude,
- Kamila Czene,
- Peter Devilee,
- HEBON investigators,
- Susan M. Domchek,
- Alison M. Dunning,
- Christoph Engel,
- D. Gareth Evans,
- Manuela Gago-Dominguez,
- Montserrat García-Closas,
- Anne-Marie Gerdes,
- Gord Glendon,
- Pascal Guénel,
- Eric Hahnen,
- Ute Hamann,
- Helen Hanson,
- Maartje J. Hooning,
- Reiner Hoppe,
- Louise Izatt,
- Anna Jakubowska,
- Paul A. James,
- Vessela N. Kristensen,
- Fiona Lalloo,
- Geoffrey J. Lindeman,
- Arto Mannermaa,
- Sara Margolin,
- Susan L. Neuhausen,
- William G. Newman,
- Paolo Peterlongo,
- Kelly-Anne Phillips,
- Miquel Angel Pujana,
- Johanna Rantala,
- Karina Rønlund,
- Emmanouil Saloustros,
- Rita K. Schmutzler,
- Andreas Schneeweiss,
- Christian F. Singer,
- Maija Suvanto,
- Yen Yen Tan,
- Manuel R. Teixeira,
- Mads Thomassen,
- Marc Tischkowitz,
- Vishakha Tripathi,
- Barbara Wappenschmidt,
- Emily Zhao,
- Douglas F. Easton,
- Antonis C. Antoniou,
- Georgia Chenevix-Trench,
- Paul D. P. Pharoah,
- Marjanka K. Schmidt,
- Carl Blomqvist,
- Heli Nevanlinna
Affiliations
- Taru A. Muranen
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki
- Anna Morra
- Division of Molecular Pathology, The Netherlands Cancer Institute
- Sofia Khan
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki
- Daniel R. Barnes
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Manjeet K. Bolla
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Joe Dennis
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Renske Keeman
- Division of Molecular Pathology, The Netherlands Cancer Institute
- Goska Leslie
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Michael T. Parsons
- Population Health Division, QIMR Berghofer Medical Research Institute
- Qin Wang
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Thomas U. Ahearn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services
- Kristiina Aittomäki
- Department of Medical and Clinical Genetics, University of Helsinki
- Irene L. Andrulis
- Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto
- Banu K. Arun
- Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center
- Sabine Behrens
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Katarzyna Bialkowska
- Department of Genetics and Pathology, Pomeranian Medical University
- Stig E. Bojesen
- Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Nicola J. Camp
- Department of Internal Medicine and Huntsman Cancer Institute, University of Utah
- Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Kamila Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Peter Devilee
- Department of Pathology, Leiden University Medical Center
- HEBON investigators
- Susan M. Domchek
- Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania
- Alison M. Dunning
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge
- Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig
- D. Gareth Evans
- Prevent Breast Cancer Research Unit, The Nightingale Centre, Manchester University Hospital Foundation NHS Trust
- Manuela Gago-Dominguez
- Health Research Institute of Santiago de Compostela Foundation (FIDIS), SERGAS, Cancer Genetics and Epidemiology Group Santiago de Compostela
- Montserrat García-Closas
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services
- Anne-Marie Gerdes
- Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital
- Gord Glendon
- Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto
- Pascal Guénel
- Team “Exposome and Heredity”, CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ
- Eric Hahnen
- Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne
- Ute Hamann
- Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)
- Helen Hanson
- SouthWest Thames Centre for Genomics, St George’s University Hospital’s NHS Foundation Trust
- Maartje J. Hooning
- Department of Medical Oncology, Erasmus MC Cancer Institute
- Reiner Hoppe
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
- Louise Izatt
- Clinical Genetics, Guy’s and St Thomas’ NHS Foundation Trust
- Anna Jakubowska
- Department of Genetics and Pathology, Pomeranian Medical University
- Paul A. James
- Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne
- Vessela N. Kristensen
- Department of Medical Genetics, Oslo University Hospital and University of Oslo
- Fiona Lalloo
- Clinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals Foundation Trust
- Geoffrey J. Lindeman
- Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne
- Arto Mannermaa
- Translational Cancer Research Area, University of Eastern Finland
- Sara Margolin
- Department of Oncology, Stockholm South General Hospital (Södersjukhuset)
- Susan L. Neuhausen
- Department of Population Sciences, Beckman Research Institute of City of Hope
- William G. Newman
- Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre
- Paolo Peterlongo
- Genome Diagnostics Program, IFOM ETS - The AIRC Institute of Molecular Oncology
- Kelly-Anne Phillips
- Department of Medical Oncology, Peter MacCallum Cancer Center, Melbourne
- Miquel Angel Pujana
- Translational Research Laboratory, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, CIBERONC
- Johanna Rantala
- Clinical Genetics, Karolinska Institutet
- Karina Rønlund
- Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle Hospital
- Emmanouil Saloustros
- Department of Oncology, University Hospital of Larissa
- Rita K. Schmutzler
- Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne
- Andreas Schneeweiss
- National Center for Tumor Diseases, University Hospital and German Cancer Research Center
- Christian F. Singer
- Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna
- Maija Suvanto
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki
- Yen Yen Tan
- Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna
- Manuel R. Teixeira
- Department of Genetics, Portuguese Oncology Institute
- Mads Thomassen
- Department of Clinical Genetics, Odense University Hospital
- Marc Tischkowitz
- Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge
- Vishakha Tripathi
- Clinical Genetics, Guy’s and St Thomas’ NHS Foundation Trust
- Barbara Wappenschmidt
- Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne
- Emily Zhao
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Douglas F. Easton
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Antonis C. Antoniou
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Georgia Chenevix-Trench
- Cancer Division, QIMR Berghofer Medical Research Institute
- Paul D. P. Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge
- Marjanka K. Schmidt
- Division of Molecular Pathology, The Netherlands Cancer Institute
- Carl Blomqvist
- Department of Oncology, Helsinki University Hospital, University of Helsinki
- Heli Nevanlinna
- Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki
- DOI
- https://doi.org/10.1038/s41523-023-00546-x
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 15
Abstract
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.
