Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction

• Published in: Breast (Edinburgh) Vol. 73; p. 103615
• Main Authors: Tüchler, Anja, De Pauw, Antoine, Ernst, Corinna, Anota, Amélie, Lakeman, Inge M.M., Dick, Julia, van der Stoep, Nienke, van Asperen, Christi J., Maringa, Monika, Herold, Natalie, Blümcke, Britta, Remy, Robert, Westerhoff, Anke, Stommel-Jenner, Denise J., Frouin, Eléonore, Richters, Lisa, Golmard, Lisa, Kütting, Nadine, Colas, Chrystelle, Wappenschmidt, Barbara, Rhiem, Kerstin, Devilee, Peter, Stoppa-Lyonnet, Dominique, Schmutzler, Rita K., Hahnen, Eric
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-02-2024; Elsevier
• Subjects: Breast cancer; Cancer prevention; Genetic testing; Hereditary breast and ovarian cancer syndrome; Original; Hereditary breast and ovarian cancer syndrome; Cancer prevention; Breast cancer; Genetic testing
• ISSN: 0960-9776; 1532-3080
• DOI: 10.1016/j.breast.2023.103615

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.
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.
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 <30 years, and women tested non-informative/negative for whom IBS may be postponed.
For women who tested non-informative/negative, PRS and NGRFs have a considerable impact on IBS recommendations. Combined consideration of eLTRs and e10YRs allows personalizing IBS starting age.
Horizon 2020, German Cancer Aid, Federal Ministry of Education and Research, Köln Fortune.
•Breast cancer (BC) risk prediction considers cancer family history and germline pathogenic variants (PVs).•Polygenic risk score (PRS) and non-genetic risk factors (NGRFs) may affect intensified breast surveillance (IBS) recommendations.•For women without PVs, PRS and NGRFs considerably impact IBS recommendations.•Comprehensive risk calculation may personalize IBS starting ages.