Polygenic risk score-based comprehensive assessment model for breast cancer risk and its application for preimplantation embryo selection in a BRCA1 mutation carrier

Using genetic data from 18,483 female breast cancer cases and 246,222 controls in the UK Biobank, and incorporating Asian ancestry–specific single nucleotide polymorphism weights, we constructed a breast cancer polygenic risk score (PRS) 313 model. Subsequently, a Cox proportional hazards regression model was developed to integrate the PRS313 model, pathogenic variants in breast cancer susceptibility genes (BRCA1 and BRCA2), and a first-degree family history of breast cancer, enabling a comprehensive risk assessment for breast cancer. In a patient from a BRCA1-positive breast cancer family who required assisted reproductive technology, we assessed each embryo for BRCA1 pathogenic variants, breast cancer PRS313 score, and family history information to obtain a comprehensive breast cancer risk estimate. Based on these assessments, together with chromosomal testing results and embryonic development status, the most suitable embryo was selected for transfer. The patient achieved a successful pregnancy and delivered a live-born infant negative for the BRCA1 variant.