PRS-BC313 integration for tailored breast cancer prevention in female patients and their healthy relatives.

Precise breast cancer risk assessment (BCR) is essential for personalised prevention in women with a family history of hereditary breast and ovarian cancer (HBOC). The CanRisk model integrates monogenic variants with reproductive, lifestyle and familial factors and can be extended by Polygenic Risk Scores (PRS). We evaluated the impact of PRS-BC313 in three groups: (1) healthy carriers of (likely) pathogenic variants (LP/P), (2) affected LP/P carriers and (3) healthy female relatives from variant-negative HBOC families.In healthy LP/P carriers, median 10-year breast cancer (BC) risk remained stable, while individual estimates ranged from+25% to -16% compared with calculations without PRS. Among affected LP/P carriers, contralateral BC risk shifted by+24% to -11%, indicating PRS effects even in high-risk individuals.In healthy relatives, applying the recently introduced German threshold of an 8% BC risk between ages 40 and 50 years resulted in escalation to intensified surveillance in ~6% (5/86) (2.4-14%, Wilson binomial CI with Yates' correction) and de-escalation in ~1% (1/86) (0.061-7.2%).Here, we provide new evidence of PRS clinical impact under the updated German threshold.