1. PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants
- Author
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Taru Muranen, Anna Morra, Sofia Khan, Daniel Barnes, Manjeet Bolla, Joe Dennis, Renske Keeman, Goska Leslie, Michael Parsons, Qin Wang, Thomas Ahearn, Kristiina Aittomäki, Irene Andrulis, Banu Arun, Sabine Behrens, Katarzyna Białkowska, Stig Bojesen, Nicola Camp, Jenny Chang-Claude, Kamila Czene, Peter Devilee, Susan Domchek, Alison Dunning, Christoph Engel, Gareth Evans, Manuela Gago-Dominguez, Montserrat Garcia-Closas, Anne-Marie Gerdes, Gord Glendon, Pascal Guénel, Eric Hahnen, Prof U. Hamann, Helen Hanson, Maartje Hooning, Reiner Hoppe, Louise Izatt, Anna Jakubowska, Paul James, Vessela Kristensen, Fiona Lalloo, Geoffrey Lindeman, Arto Mannermaa, Sara Margolin, Susan Neuhausen, William Newman, Paolo Peterlongo, Kelly-Anne Phillips, Miquel Angel Pujana, Johann Rantala, Karina Rønlund, Emmanouil Saloustros, Rita Schmutzler, andreas schneeweiss, Christian Singer, Maija Suvanto, Yen Yen Tan, Manuel Teixeira, Mads Thomassen, Marc Tischkowitz, Vishakha Tripathi, Barbara Wappenschmidt, Emily Zhao, Douglas Easton, Antonis Antoniou, Georgia Chenevix-Trench, Paul Pharoah, Marjanka Schmidt, Carl Blomqvist, and Heli Nevanlinna
- 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 under-estimated at the low end of the PREDICT score distribution, whereas at the high end, the mortality was over-estimated. 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.
- Published
- 2022