Introduction

An international coalition of experts has taken a monumental step in the realm of breast cancer prevention by releasing the very first evidence-based clinical guidance on the application of polygenic risk scores (PRSs). This pioneering guidance was published in the journal *Cancers* and provides healthcare professionals with essential recommendations for incorporating PRS testing into standard healthcare practices, ultimately tailoring prevention efforts and screening protocols to individual risk profiles.

Understanding Polygenic Risk Scores

Polygenic risk scores assess an individual’s genetic predisposition to diseases, taking into account numerous common genetic variants. In the context of breast cancer, these scores can stratify women's hereditary risk levels, facilitating early detection, targeted preventive measures, and personalized screening timelines. This is particularly crucial as breast cancer remains one of the most common cancers affecting women worldwide.

A Transformative Moment for Personalized Medicine

Despite extensive research around PRSs, there was a significant gap in international clinical guidance regarding their application in healthcare until now. "This represents a transformative moment for personalized medicine in breast cancer," emphasized Dr. Peeter Padrik, MD PhD, the lead author and an oncologist at Tartu University Hospital. "With PRS testing, clinicians are empowered to implement proactive and personalized preventive strategies for women identified as high-risk – long before any clinical symptoms manifest."

Clinical Significance of the Guidance

Dr. Gareth Evans, MD, FRCP, senior author and a Professor of Medical Genetics at the University of Manchester, further elaborated on the significance of this guidance. He noted that PRSs serve as a complement to existing genetic testing methods—helping to identify risk in women without rare genetic mutations such as those found in the BRCA1 or BRCA2 genes, or without notable family histories of the disease. "Our guidance provides healthcare systems a coherent framework to leverage PRS data for enhanced prevention and screening programs," he stated.

Recommendations and Best Practices

The newly published guidance outlines specific clinical scenarios for PRS testing, recommending its use among healthy women—irrespective of their family histories—within hereditary cancer clinics and as part of population-based breast cancer screening initiatives. It also outlines best practices for interpreting PRS results, suggesting that these should be integrated with established risk prediction models, like CanRisk and Tyrer–Cuzick, to boost the precision of individual risk assessments.

Alignment with National Guidelines

Furthermore, the recommendations align with current national healthcare guidelines, such as those set forth by the UK's NICE and practices observed in Germany, Sweden, Norway, Portugal, and Estonia. Importantly, the guidance takes into account regulatory concerns under the EU's In Vitro Diagnostic Medical Devices Regulation (IVDR), underscoring the necessity for equitable access and effective implementation across diverse populations.

Broader Implications for Preventive Practices

Dr. Sander Pajusalu, MD, PhD, a clinical geneticist and Head of the Genetics and Personalized Medicine Clinic at Tartu University Hospital, emphasized the larger implications of integrating PRS into risk assessments. "This guidance is a pivotal step in embedding genomic insights into routine preventive practices. Polygenic risk scores enable us to evaluate the genetic risk of breast cancer in a broader cohort, ensuring that preventive interventions, like mammography screenings, are focused on the individuals who will benefit the most."

Responding to Critiques

Additionally, this guidance responds to prior critiques from the American College of Medical Genetics and Genomics (ACMG), which had pointed out the absence of structured frameworks for PRS usage in clinical settings. By identifying practical scenarios and applications of PRS testing, the expert group supports a responsible and evidence-focused rollout of this innovative approach globally.

Research Collaboration and Future Outlook

The team behind this transformational guidance includes leading researchers and clinicians from the BRIGHT and AnteNOR projects, which have been at the forefront of integrating PRS testing into breast cancer prevention strategies. As the medical community looks forward, this initiative could redefine the landscape of breast cancer care and significantly improve patient outcomes through personalized medicine.

Conclusion

Stay tuned as this unfolding narrative develops, potentially changing the course of breast cancer prevention forever!