1562P - The feasibility of polygenic risk score-based population screening for breast cancer: The experience from the BRIGHT study in Estonia

Background

Breast cancer (BC) is the leading cause of cancer deaths in women. Current BC screening includes women over 50, but up to 20% of all BCs occur in younger women. Moreover, current mammography-based BC screening addresses up to 58% of all BC cases. Therefore, there is a need for new preventative screening strategies that are also cost-effective. In an international Be RIGHT with breast cancer risk management (BRIGHT) study, we used a polygenic risk score (PRS)-based screening to identify high-risk women in a population that does not attend routine mammography to show that PRS-based BC screening is cost-effective and has clinical utility.

Methods

In Estonia, 799 participants aged 35-49 were enrolled in the study between 2022-2023. For PRS testing, the AnteBC test (Antegenes OÜ) was used. The PRS was calculated based on 2803 BC-related genetic variants. Participants also self-filled a questionnaire about previous family cancer history for monogenic pathogenic variant (MPV) testing. All participants received a report with relevant clinical recommendations based on PRS levels. Both participants and investigators had the opportunity to fill in online feedback questionnaires.

Results

Based on PRS testing, 15.9% needed to start BC screening earlier and 58.8% according to national guidelines. From attended mammographies (154), 127 had no and 16 had benign findings. Five biopsies were taken and one stage 0 in situ intraductal BC was diagnosed. 80 participants received MPV testing, 5.7% had disease-related genetic findings. 98.3% of participants agreed that information provided was clear and sufficient, and 71.4% said they were coping well with knowing their genetic risks. 89% of investigators agreed that genetic risk in BC prevention is important based on the experience gained in BRIGHT study. 61% of investigators would definitely use the AnteBC test in clinical practice, time and need for extra knowledge were brought out as limiting factors.

Conclusions

The results of the BRIGHT study in Estonia indicate that PRS-based BC screening is feasible, has clinical utility and healthcare systems are ready for implementation. In Estonia, the addition of PRS into BC screening is planned within next few years.

Clinical trial identification

The BRIGHT study has been registered in the ISRCTN registry under ID ISRCTN29884654. Registration date 13.01.2023.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

European Commission via EIT Health (project #220720) and the Estonian Research Council PRG555 grant.

Disclosure

P. Padrik: Financial Interests, Institutional, Leadership Role: OÜ Antegenes. A. Paas, K. Kruuv-Käo, S. Sõber, A. Padrik, J. Pindmaa, Financial Interests, Institutional, Full or part-time Employment: OÜ Antegenes. All other authors have declared no conflicts of interest.