Polygenic Risk Score (PRS) Combined with NGS Panel Testing Increases Accuracy in Hereditary Breast Cancer Risk...

Area of Science:

• Oncology
• Genetics
• Epidemiology

Background:

• Breast cancer (BC) is a leading cancer in women, with risk factors including genetics and family history.
• In many cases, the exact cause of BC remains unknown, suggesting a polygenic component.
• Polygenic Risk Score (PRS) estimates BC susceptibility based on multiple genetic variants.

Purpose of the Study:

• To retrospectively evaluate the clinical utility of integrating PRS into BC risk assessment.
• To analyze PRS in a cohort of diagnosed breast cancer patients with existing genetic and family history data.

Main Methods:

• Retrospective analysis of 105 breast cancer patients with Next-Generation Sequencing (NGS) results.
• PRS calculation using an external laboratory (Allelica).
• Risk assessment computed with and without PRS, considering gene status and family history (FH).

Main Results:

• The patient cohort showed a significantly higher PRS distribution compared to the general population.
• Elevated PRS-based risk was noted in younger patients and those with a family history of cancer.
• In patients with pathogenic germline variants, PRS values were lower, with monogenic etiology dominating risk.
• Incorporating PRS identified elevated BC susceptibility in 41.90% of patients.
• PRS increased risk detection by 63.63% in patients with a family history but no detected pathogenic variant.

Conclusions:

• PRS calculation is highly useful for women with a family history of BC but no identified monogenic cause via NGS.
• Combining genetic testing, family history, and PRS improves breast cancer risk stratification.
• Enhanced risk stratification can lead to more effective preventive strategies and optimized healthcare resource allocation.