164P Incorporation of the polygenic risk score (PRS) in breast cancer (BC) risk estimation among carriers of a moderate penetrance pathogenic variant (MPPV)

• DOI: 10.1016/j.esmoop.2024.103186
• Publication Date: 2024-05-17T11:20:07Z
• Authors: M.A. Rezqallah Aron; L. Duran-Lozano; A. López-Fernández; E. Darder; R. Alfonso; M. Cartró; A.R. Jiménez-Macedo; A. Bareas; M. Cruellas Lapena; A. Moles-Fernández; M. Torres; A. Vallmajó; G. Llort Pursals; A. Roqué Lloveras; C. Llorente; M. Espinosa-Bravo; N. Tuset; T. Ramon y Cajal; J.M. Brunet Vidal; J. Balmaña Gelpi
• Keywords: Penetrance; Polygenic risk score

Women with MPPV in BC genes have broad risk estimates. Follow-up and prevention guidelines often employ a one-size-fits-all approach. However, the PRS may help stratify risk. We aimed to evaluate change stratification when adding classical factors healthy women harboring MPPV. Multicentric study of aged 30-70 germline pathogenic variant PALB2, CHEK2, ATM, BARD1, or RAD51C/D available breast density (BD). Genotyping employed PRiSma-268 array. Cumulative 10-year was calculated using BOADICEA v.6 model: baseline model included personal, family history, BD; full incorporated PRS. categorized as average, moderate, high based on NICE (<3%, 3-8%, >8%, respectively). Descriptive statistics were used. 133 median age 49 years (30–67.5), most variants ATM (36%), PALB2 (24%), CHEK2 (20.3%). Median Z score 0.27 [-2.72–3.45], highest (0.89 [-1.83-2.44]) lowest RAD51C (-0.21 [-1.31-3.45]). Overall, 6% [0.7–22.7] 5.6% [2.6–22.7] model. After PRS, group classification shifted 28% women, 15% increasing 13% decreasing their respective categories. In RAD51C, 23% 56% average results should be interpreted caution due limited sample size (Table).Table: 164PGeneAll carriersPALB2ATMCHEK2BARD1RAD51CRAD51DN (%)133 (100)32 (24)48 (36)27 (20,3)5 (3,7)16 (12)5 (3,7)Median age49 [30-67,5]47,1 [30,7-64,3]50 [36,8-68,1]49 [32,2-62]46,6 [42,9-65,1]56,5 [32,4-66,9]43,1 [33,1-62]Median score0,27 [-2,7-3,4]0,01 [-2,5-1,9]0,06 [-2,7-3,1]0,89 [-1,8-2,4]0,49 [0,5-0,8]-0,21[-1,3-3,4]0,40 [0,01-1,7]Basal/Full (%) Average Moderate High17/20,354/44,329/35,33/628/2569/6912,5/2375/5212,5/2530/1537/5233/330/060/6040/4037,5/5662,5/380/620/2080/600/20Total Increase Decrease Stable27,81512,872,228,112,515,671,931,316,714,668,822,214,87,477,800010037,512,52562,52020080 Open table new tab Adding estimation carriers significantly modifies stratification, which provide valuable information for making informed decisions regarding preventive measures screening strategies.