Abstract 164P
Background
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 the risk. We aimed to evaluate the change in risk stratification when adding the PRS to the classical BC risk factors in healthy women harboring a MPPV.
Methods
Multicentric study of women aged 30-70 with a germline pathogenic variant in PALB2, CHEK2, ATM, BARD1, or RAD51C/D and available breast density (BD). Genotyping employed the PRiSma-268 array. Cumulative 10-year risk was calculated using the BOADICEA v.6 model: the baseline model included personal, family history, and BD; and the full model incorporated the PRS. BC risk was categorized as average, moderate, and high based on NICE guidelines (<3%, 3-8%, >8%, respectively). Descriptive statistics were used.
Results
We included 133 women with a median age of 49 years (30–67.5), with most harboring pathogenic variants in ATM (36%), PALB2 (24%), and CHEK2 (20.3%). Median Z score was 0.27 [-2.72–3.45], with the highest in CHEK2 (0.89 [-1.83-2.44]) and the lowest in RAD51C (-0.21 [-1.31-3.45]). Overall, median 10-year risk was 6% [0.7–22.7] in the baseline model and 5.6% [2.6–22.7] in the full model. After adding the PRS, risk group classification shifted in 28% of women, with 15% increasing and 13% decreasing their respective categories. In ATM and RAD51C, 23% and 56% of women were categorized as average risk with the full model. However, results should be interpreted with caution due to the limited sample size (Table). Table: 164P
| Gene | All carriers | PALB2 | ATM | CHEK2 | BARD1 | RAD51C | RAD51D |
| N (%) | 133 (100) | 32 (24) | 48 (36) | 27 (20,3) | 5 (3,7) | 16 (12) | 5 (3,7) |
| Median age | 49 [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 Z score | 0,27 [-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 model (%) Average Moderate High | 17/20,354/44,329/35,3 | 3/628/2569/69 | 12,5/2375/5212,5/25 | 30/1537/5233/33 | 0/060/6040/40 | 37,5/5662,5/380/6 | 20/2080/600/20 |
| Total risk group change (%) Increase Decrease Stable | 27,81512,872,2 | 28,112,515,671,9 | 31,316,714,668,8 | 22,214,87,477,8 | 000100 | 37,512,52562,5 | 2020080 |
Conclusions
Adding the PRS to BC risk estimation in carriers of MPPV significantly modifies BC risk stratification, which may provide valuable information for making informed decisions regarding preventive measures and screening strategies.
Legal entity responsible for the study
The authors.
Funding
ISCIII (PI23/01047) and BCRF.
Disclosure
C. Llorente: Non-Financial Interests, Institutional, Other, Participated as a researcher in a Randomized Clinical Trial to assess the efficacy and safety of a vaccine for the prevention of SARS-COV-2-sponsored by Janssen: Janssen Company. T. Ramon y Cajal: Financial Interests, Institutional, Other, CI advisor: Lilly; Financial Interests, Personal, Other, travel expensas and congress registration: Pfizer. J. Balmaña Gelpi: Other, Personal, Invited Speaker: AstraZeneca; Other, Institutional, Other, Educational programs: AstraZeneca -MSD; Financial Interests, Institutional, Other, Steering Committee Membe: AstraZeneca; Financial Interests, Institutional, Other, Local PI, Financial interest: MedSir. All other authors have declared no conflicts of interest.