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William J. Gradishar, MD, FACP, FASCO


Predictive Ability of Ancestry-Adjusted Polygenic Risk Scores for Breast Cancer

By: Victoria Kuhr, BA
Posted: Tuesday, July 25, 2023

Daniel Morganstern, MD, of Hartford Healthcare Cancer Institute, and colleagues observed that polygenic risk scores may be optimized for genetic ancestries and integrated into breast cancer risk models to improve risk stratification of treatments. This finding, which was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 10506), may enable more targeted screening and prevention strategies to improve the cost/benefit ratio in this patient population.

The researchers built and validated an ancestry-specific breast cancer polygenic risk score model. The model employed methodologies leveraged from multiple genome-wide association studies and linkage disequilibrium maps. The study analyzed the genetic ancestry from five continental-level ancestry groups that spanned all individuals in the study. Additionally, the study applied the polygenic risk score model to assess the clinical implications of integrating genetic information to the Tyrer-Cuzick (TC) breast cancer risk model. The net reclassification improvement (NRI) was calculated using 0% to 15%, 15% to 20%, and more than 20% as risk categories.

The study included a total of 177,253 ancestry controls and 10,774 cases and contained African (n = 4,579), Admixed American (n = 1,645), East Asian (n = 1,674), European (n = 165,044), and South Asian (n = 4,311) ancestries. Researchers observed that the polygenic risk scores were well calibrated and displayed high risk stratification. These results were found to be comparable or better than benchmarking comparisons with previously published polygenic risk score panels.

Across genetic ancestries, the integration of polygenic risk scores led to a relative increased number in women identified as having a high lifetime risk of breast cancer (20% or higher). The at-risk women ranged from between 1.7-fold of women with East Asian ancestry to approximately 3-fold of women with European ancestry. The NRI of the polygenic risk score model compared with the TC breast cancer model was approximately 12% for East Asian, European, and Admixed American ancestries; 17% for South Asian ancestry; and 5% for African ancestry individuals.

Disclosure: Dr. Morganstern reported no conflicts of interest. For full disclosures of the other study authors, visit

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