PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in ~ 200,000 patients
Year: 2022
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Prediction of contralateral breast cancer (CBC) risk is challenging due to moderate performances of the known risk factors. We aimed to improve our previous risk prediction model (PredictCBC) by updated follow-up and including additional risk factors. METHODS: We included data from 207,510 invasive breast cancer patients participating in 23 studies. In total, 8225 CBC events occurred over a median follow-up of 10.2 years. In addition to the previously included risk factors, PredictCBC-2.0 included CHEK2 c.1100delC, a 313 variant polygenic risk score (PRS-313), body mass index (BMI), and parity. Fine and Gray regression was used to fit the model. Calibration and a time-dependent area under the curve (AUC) at 5 and 10 years were assessed to determine the performance of the models. Decision curve analysis was performed to evaluate the net benefit of PredictCBC-2.0 and previous PredictCBC models. RESULTS: The discrimination of PredictCBC-2.0 at 10 years was higher than PredictCBC with an AUC of 0.65 (95% prediction intervals (PI) 0.56-0.74) versus 0.63 (95%PI 0.54-0.71). PredictCBC-2.0 was well calibrated with an observed/expected ratio at 10 years of 0.92 (95%PI 0.34-2.54). Decision curve analysis for contralateral preventive mastectomy (CPM) showed the potential clinical utility of PredictCBC-2.0 between thresholds of 4 and 12% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS: Additional genetic information beyond BRCA1/2 germline mutations improved CBC risk prediction and might help tailor clinical decision-making toward CPM or alternative preventive strategies. Identifying patients who benefit from CPM, especially in the general breast cancer population, remains challenging.
Source: Breast Cancer Research
Authors: Daniele Giardiello, Maartje J. Hooning, Michael Hauptmann, Renske Keeman, B. A. M. Heemskerk-Gerritsen, Heiko Becher, Carl Blomqvist, Stig E. Bojesen, Manjeet K. Bolla, Nicola J. Camp, Kamila Czene, Peter Devilee, Diana M. Eccles, Peter A. Fasching, Jonine D. Figueroa, Henrik Flyger, Montserrat García-Closas, Christopher A. Haiman, Ute Hamann, John L. Hopper, Anna Jakubowska, Floor E. Leeuwen, Annika Lindblom, Jan Lubiński, Sara Margolin, Maria Elena Martinez, Heli Nevanlinna, Ines Nevelsteen, Saskia Pelders, Paul D. P. Pharoah, Sabine Siesling, Melissa C. Southey, Annemieke H. van der Hout, Liselotte P. van Hest, Jenny Chang-Claude, Per Hall, Douglas F. Easton, Ewout W. Steyerberg, Marjanka K. Schmidt
Institutions: Eurac Research, Leiden University Medical Center, The Netherlands Cancer Institute, Institute for Biomedicine, University of Lübeck, Erasmus MC Cancer Institute, Medizinische Hochschule Brandenburg Theodor Fontane, University Medical Center Hamburg-Eppendorf, University of Helsinki, Helsinki University Hospital, Örebro University Hospital, University of Copenhagen, Herlev Hospital, Copenhagen University Hospital, Gentofte Hospital, University of Cambridge, University of Utah, Huntsman Cancer Institute, Karolinska Institutet, University of Southampton, University of California, Los Angeles, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen, National Institutes of Health, Edinburgh Cancer Research, National Cancer Institute, Division of Cancer Epidemiology and Genetics, University of Edinburgh, University of Southern California, German Cancer Research Center, The University of Melbourne, Pomeranian Medical University, Karolinska University Hospital, Stockholm South General Hospital, University of California San Diego, Moores Cancer Center, Universitair Ziekenhuis Leuven, Netherlands Comprehensive Cancer Organisation, University of Twente, Cancer Council Victoria, Monash Health, Monash University, University Medical Center Groningen, University of Groningen, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, University Cancer Center Hamburg
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,590
Funders: U.S. Department of Health and Human Services, Intermountain Healthcare, University of Southern California, University of Utah, Deutsches Krebsforschungszentrum, Huntsman Cancer Foundation, Huntsman Cancer Institute, Amsterdam University Medical Centers, Cancer Research UK, Breast Cancer Campaign, University of Southampton, European Commission, University of Edinburgh, Universiteit Leiden, Rijksuniversiteit Groningen, University of Melbourne, Radboud Universiteit, Vrije Universiteit Amsterdam, Universiteit Maastricht, Bundesministerium für Bildung und Forschung, Cancerfonden, Gentofte Hospital, Erasmus Medisch Centrum, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Ministerio de Economía y Competitividad, Ministerio de Sanidad, Servicios Sociales e Igualdad, Karolinska Institutet, Stockholms Läns Landsting, Maastricht Universitair Medisch Centrum, KWF Kankerbestrijding, Leids Universitair Medisch Centrum, Deutsche Krebshilfe, Radboud Universitair Medisch Centrum, Pomorski Uniwersytet Medyczny W Szczecinie, Xunta de Galicia, National Institutes of Health, Centers for Disease Control and Prevention, Medical Research Council, National Health and Medical Research Council, Instituto de Salud Carlos III, Servicio Gallego de Salud, National Cancer Institute, David Geffen School of Medicine, University of California, Los Angeles
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OpenAlex ID: W4307048188