International group publishes first clinical guidance on polygenic risk scores for breast cancer

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An international expert group has released the first evidence-based clinical guidance on the use of polygenic risk scores (PRSs) for breast cancer. Published in Cancers, the guidance provides recommendations for integrating PRS testing into routine health care for personalized breast cancer prevention and screening.^1,2

Polygenic risk scores calculate an individual’s susceptibility to disease based on multiple common genetic variants. In breast cancer, PRSs help stratify women by inherited risk levels, aiding in early detection, preventive strategies, and tailored screening schedules.

While PRSs have been widely studied, no international clinical guidance previously outlined their use in healthcare. “This is a landmark step for personalised medicine in breast cancer,” said Peeter Padrik, MD PhD, lead author and oncologist at Tartu University Hospital and founder and CEO of Antegenes. “PRS testing empowers clinicians to offer earlier and more tailored prevention to women at higher risk – well before any symptoms appear.”

Gareth Evans, MD, FRCP, senior author and Professor of Medical Genetics at the University of Manchester, highlighted that PRSs complement existing genetic testing by identifying risk in women who do not carry rare pathogenic variants in genes like BRCA1 or BRCA2 or have a strong family history. “This guidance gives healthcare systems a structured way to use PRS information for more effective prevention and screening,” he said.

The guidance outlines clinical indications for PRS testing, including use among healthy women with or without a family history of breast cancer, in hereditary cancer clinics, and within population-based screening programs.

It also provides recommendations for interpreting PRS test results and integrating them with established risk prediction models such as CanRisk and Tyrer–Cuzick to improve individual risk assessment accuracy.

Additionally, the recommendations align with existing national guidelines, including the UK’s NICE guidelines and clinical practices in Germany, Sweden, Norway, Portugal, and Estonia.

The guidance also addresses regulatory considerations under the EU In Vitro Diagnostic Medical Devices Regulation (IVDR) and emphasizes the need for equitable access and performance across diverse populations.

Sander Pajusalu, MD, PhD, clinical geneticist and Head of the Genetics and Personalised Medicine Clinic at Tartu University Hospital, noted the significance of integrating PRS testing into risk assessment. “This guidance marks an important milestone in bringing genomics into routine preventive care. Polygenic risk scores give us the opportunity to assess the genetic risk of breast cancer in more women than before – ensuring that preventive measures, such as mammography screening, are targeted to those who need them the most.”

The guidance also responds to concerns from the American College of Medical Genetics and Genomics (ACMG), which has previously highlighted the lack of clinical frameworks for PRS use. By defining clinical scenarios and practical use cases, it supports responsible and evidence-based implementation of PRS testing worldwide.

The expert group behind the article includes researchers and clinicians from the BRIGHT and AnteNOR research projects, which have pioneered the clinical use of PRS testing for breast cancer prevention, according to a press release. .

References:

1. Estonian Research Council. First international clinical guidance on breast cancer polygenic risk scores published. Eurekalert. April 1, 2025, Accessed April 1, 2025. https://www.eurekalert.org/news-releases/1078989

2. Padrik P, Tõnisson N, Hovda T, Sahlberg KK, Hovig E, Costa L, Nogueira da Costa G, Feldman I, Sampaio F, Pajusalu S, et al. Guidance for the Clinical Use of the Breast Cancer Polygenic Risk Scores. Cancers. 2025; 17(7):1056. https://doi.org/10.3390/cancers17071056