학술논문
Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction
Document Type
article
Author
Anja Tüchler; Antoine De Pauw; Corinna Ernst; Amélie Anota; Inge M.M. Lakeman; Julia Dick; Nienke van der Stoep; Christi J. van Asperen; Monika Maringa; Natalie Herold; Britta Blümcke; Robert Remy; Anke Westerhoff; Denise J. Stommel-Jenner; Eléonore Frouin; Lisa Richters; Lisa Golmard; Nadine Kütting; Chrystelle Colas; Barbara Wappenschmidt; Kerstin Rhiem; Peter Devilee; Dominique Stoppa-Lyonnet; Rita K. Schmutzler; Eric Hahnen
Source
Breast, Vol 73, Iss , Pp 103615- (2024)
Subject
Language
English
ISSN
1532-3080
Abstract
Background: Breast cancer (BC) risk prediction models consider cancer family history (FH) and germline pathogenic variants (PVs) in risk genes. It remains elusive to what extent complementation with polygenic risk score (PRS) and non-genetic risk factor (NGRFs) data affects individual intensified breast surveillance (IBS) recommendations according to European guidelines. Methods: For 425 cancer-free women with cancer FH (mean age 40·6 years, range 21–74), recruited in France, Germany and the Netherlands, germline PV status, NGRFs, and a 306 variant-based PRS (PRS306) were assessed to calculate estimated lifetime risks (eLTR) and estimated 10-year risks (e10YR) using CanRisk. The proportions of women changing country-specific European risk categories for IBS recommendations, i.e. ≥20 % and ≥30 % eLTR, or ≥5 % e10YR were determined. Findings: Of the women with non-informative PV status, including PRS306 and NGRFs changed clinical recommendations for 31·0 %, (57/184, 20 % eLTR), 15·8 % (29/184, 30 % eLTR) and 22·4 % (41/183, 5 % e10YR), respectively whereas of the women tested negative for a PV observed in their family, clinical recommendations changed for 16·7 % (25/150), 1·3 % (2/150) and 9·5 % (14/147). No change was observed for 82 women with PVs in high-risk genes (BRCA1/2, PALB2). Combined consideration of eLTRs and e10YRs identified BRCA1/2 PV carriers benefitting from IBS