Background/Objectives: Polygenic risk scores (PRSs) have been extensively studied and are increasingly applied in healthcare. One of the most studied and developed areas is predictive medicine for breast cancer, but there is no wider consensus on the indications for the clinical use of PRSs for breast cancer. This current guidance endeavours to articulate the scientific evidence underpinning the clinical utility of PRSs in stratifying breast cancer risk, with a particular emphasis on clinical application.

Methods: This guidance has been prepared by a group of experts who have been active in breast cancer PRS research and development, combining a review of the evidence base with expert opinion for indications for clinical use.

Results: Based on data from various studies and existing breast cancer prevention and screening services, the indications for clinical use of breast cancer PRSs can be divided into the following scenarios: (1) Management of cancer-free women with a family history of cancer; (2) individual personalised breast cancer prevention and screening in healthcare services; and (3) breast cancer screening programs for more personalised screening.

Conclusions: The integration of PRSs into clinical practice enables healthcare providers to deliver more accurate risk assessments, personalised prevention strategies, and optimised screening programmes, thereby improving patient outcomes and enhancing the effectiveness of breast cancer care. PRS testing represents a novel component in clinical breast cancer risk assessment, supporting a personalised, risk-based approach to breast cancer prevention and screening.